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

c.dna	Variant	SGM Consensus	Domain	ClinVar			gnomAD			ESM1b		AlphaMissense			REVEL		FoldX			Rosetta		Foldetta		PremPS		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation									DOI
				Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Score	Prediction	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.1003C>T	R335C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335C is listed in ClinVar with an uncertain significance (ClinVar ID 2835865.0) and is present in gnomAD (ID 6‑33437908‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are AlphaMissense‑Optimized, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion aligns with the ClinVar designation of uncertain significance, which does not contradict the prediction that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Uncertain		1	6-33437908-C-T	1	6.20e-7	-14.354	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.277	Likely Benign	0.53	Ambiguous	0.1	0.85	Ambiguous	0.69	Ambiguous	0.46	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.67	Pathogenic	0.01	Affected	3.38	22	-3	-4	7.0	-53.05
c.103G>A	V35I 2D AIThe SynGAP1 missense variant V35I is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33423512‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a benign outcome. No Foldetta stability data are available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33423512-G-A	5	3.10e-6	-3.764	Likely Benign	0.081	Likely Benign	Likely Benign	0.017	Likely Benign										-0.32	Neutral	0.672	Possibly Damaging	0.369	Benign	4.16	Benign	0.00	Affected	4.32	1	3	4	0.3	14.03
c.1040C>A	T347N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T347N is listed in ClinVar with an uncertain significance (ClinVar ID 3672484.0) and is present in the gnomAD database (gnomAD ID 6‑33437945‑C‑A). Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to “Likely Benign” (3 benign vs. 1 pathogenic). High‑accuracy assessments are consistent: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the collective evidence points to a benign effect, aligning with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	Uncertain		1	6-33437945-C-A	9	5.58e-6	-5.545	Likely Benign	0.165	Likely Benign	Likely Benign	0.059	Likely Benign	0.41	Likely Benign	0.1	0.46	Likely Benign	0.44	Likely Benign	-0.06	Likely Benign	1.96	Neutral	0.001	Benign	0.001	Benign	1.67	Pathogenic	0.60	Tolerated	3.37	25	0	0	-2.8	13.00
c.1058T>C	L353P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL predicts benign, whereas FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict pathogenic. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar designation of uncertain significance but leans toward pathogenicity rather than benign. Thus, the variant is most likely pathogenic, and this prediction does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Uncertain		1				-7.913	In-Between	0.936	Likely Pathogenic	Ambiguous	0.464	Likely Benign	4.63	Destabilizing	0.1	10.19	Destabilizing	7.41	Destabilizing	2.17	Destabilizing	-3.70	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.29	Pathogenic	0.02	Affected	3.37	25	-3	-3	-5.4	-16.04
c.1067G>A	R356H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R356H is recorded in ClinVar as benign (ClinVar ID 2984966.0) and is present in the gnomAD database (6‑33437972‑G‑A). Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, with the SGM‑Consensus also labeling it likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions support a pathogenic impact, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Likely Benign		1	6-33437972-G-A	9	5.66e-6	-11.453	Likely Pathogenic	0.614	Likely Pathogenic	Likely Benign	0.314	Likely Benign	0.59	Ambiguous	0.1	-0.27	Likely Benign	0.16	Likely Benign	1.17	Destabilizing	-4.43	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	1.70	Pathogenic	0.01	Affected	3.39	22	0	2	1.3	-19.05
c.106C>T	H36Y 2D AIThe SynGAP1 missense variant H36Y is listed in ClinVar with an uncertain significance (ClinVar ID 2089635.0) and is present in the gnomAD database (gnomAD ID 6‑33423515‑C‑T). Functional prediction tools largely agree that the substitution is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a benign effect. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. No Foldetta stability prediction is available. Overall, the computational evidence overwhelmingly supports a benign classification, which is consistent with the ClinVar designation of uncertain significance rather than a pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33423515-C-T	2	1.24e-6	-3.461	Likely Benign	0.139	Likely Benign	Likely Benign	0.023	Likely Benign										-1.03	Neutral	0.219	Benign	0.066	Benign	4.16	Benign	0.00	Affected	4.32	1	0	2	1.9	26.03
c.1082A>C	Q361P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361P is listed in ClinVar as Pathogenic (ClinVar ID 3235087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the overwhelming agreement of these predictions, the variant is most likely pathogenic, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Likely Pathogenic		1				-13.280	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.482	Likely Benign	3.12	Destabilizing	0.0	3.45	Destabilizing	3.29	Destabilizing	0.38	Likely Benign	-3.03	Deleterious	0.996	Probably Damaging	0.979	Probably Damaging	1.63	Pathogenic	0.05	Affected	3.37	25	-1	0	1.9	-31.01
c.1118G>A	G373E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G373E is listed in ClinVar with an Uncertain significance and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, Foldetta, SIFT, and AlphaMissense‑Default. Predictions from Rosetta and ESM1b are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as pathogenic. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	Uncertain		1				-7.281	In-Between	0.569	Likely Pathogenic	Likely Benign	0.420	Likely Benign	4.13	Destabilizing	3.2	0.52	Ambiguous	2.33	Destabilizing	-0.02	Likely Benign	-0.69	Neutral	0.001	Benign	0.000	Benign	3.90	Benign	0.01	Affected			0	-2	-3.1	72.06
c.1126G>T	G376C 2D AISynGAP1 missense variant G376C is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, premPS, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls come from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools report uncertainty: Foldetta and ESM1b. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, whereas the most accurate methods favor a benign effect. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	Uncertain		1				-7.686	In-Between	0.125	Likely Benign	Likely Benign	0.560	Likely Pathogenic	2.56	Destabilizing	0.5	0.22	Likely Benign	1.39	Ambiguous	0.16	Likely Benign	-1.15	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	1.32	Pathogenic	0.01	Affected			-3	-3	2.9	46.09
c.1131G>A	M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I (ClinVar ID 3803473.0, status = Uncertain) is present in gnomAD (ID = 6‑33438036‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the computational evidence strongly favors a benign classification, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	Uncertain		1	6-33438036-G-A	1	6.23e-7	-2.895	Likely Benign	0.212	Likely Benign	Likely Benign	0.227	Likely Benign	0.76	Ambiguous	0.3	0.54	Ambiguous	0.65	Ambiguous	0.24	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	5.46	Benign	0.26	Tolerated	4.32	12	1	2	2.6	-18.03
c.113C>T	P38L 2D AIThe SynGAP1 missense variant P38L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33423522‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. 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, 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		Conflicting		4	6-33423522-C-T	8	4.96e-6	-2.469	Likely Benign	0.197	Likely Benign	Likely Benign	0.141	Likely Benign										-2.56	Deleterious	0.983	Probably Damaging	0.931	Probably Damaging	4.02	Benign	0.00	Affected	4.32	1	-3	-3	5.4	16.04
c.1147G>T	G383W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G383W is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438052‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as benign, and Foldetta as pathogenic. Because the majority of conventional predictors favor pathogenicity while the high‑accuracy subset is split, the overall evidence leans toward a pathogenic interpretation. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	Uncertain		1	6-33438052-G-T	1	6.22e-7	-10.161	Likely Pathogenic	0.439	Ambiguous	Likely Benign	0.469	Likely Benign	5.81	Destabilizing	3.6	4.44	Destabilizing	5.13	Destabilizing	0.08	Likely Benign	-1.01	Neutral	0.959	Probably Damaging	0.704	Possibly Damaging	4.09	Benign	0.00	Affected	4.32	7	-2	-7	-0.5	129.16
c.1157G>A	G386E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G386E is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438062‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are FoldX, Foldetta, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Overall, the majority of tools predict a pathogenic impact, suggesting the variant is most likely pathogenic, which does not contradict the ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	Uncertain		1	6-33438062-G-A			-9.286	Likely Pathogenic	0.686	Likely Pathogenic	Likely Benign	0.447	Likely Benign	3.69	Destabilizing	2.9	0.79	Ambiguous	2.24	Destabilizing	0.54	Ambiguous	-0.83	Neutral	0.860	Possibly Damaging	0.354	Benign	3.93	Benign	0.01	Affected	4.32	3	-2	0	-3.1	72.06
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 (ID 6‑33438107‑G‑A). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of 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 methods reinforce the pathogenic prediction: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta’s stability assessment is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect, 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	Uncertain		1	6-33438107-G-A			-11.213	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.780	Likely Pathogenic	0.96	Ambiguous	0.1	1.50	Ambiguous	1.23	Ambiguous	1.20	Destabilizing	-3.69	Deleterious	0.999	Probably Damaging	0.978	Probably Damaging	5.47	Benign	0.04	Affected	3.38	27	1	1	1.0	-28.06
c.1214G>C	R405P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—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) indicates it is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies it as pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Uncertain		1				-14.206	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.572	Likely Pathogenic	3.11	Destabilizing	0.3	5.19	Destabilizing	4.15	Destabilizing	1.26	Destabilizing	-6.32	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.62	Benign	0.01	Affected	3.38	28	-2	0	2.9	-59.07
c.121C>T	R41C 2D AIThe SynGAP1 missense variant R41C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33423530‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and no result is available from Foldetta (protein‑folding stability). Taken together, the majority of evidence points to a benign impact for R41C, 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		Conflicting		3	6-33423530-C-T	7	4.34e-6	-4.745	Likely Benign	0.207	Likely Benign	Likely Benign	0.093	Likely Benign										-1.10	Neutral	0.976	Probably Damaging	0.919	Probably Damaging	4.13	Benign	0.00	Affected	4.32	1	-4	-3	7.0	-53.05
c.1221G>T	Q407H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q407H is listed in ClinVar with an uncertain significance (ClinVar ID 2772184.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked as uncertain include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Q407H. This conclusion does not conflict with the ClinVar designation of uncertain significance, which remains unresolved pending further evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	Uncertain		1				-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.206	Likely Benign	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0	3	0.3	9.01
c.1222A>G	T408A 2D AISynGAP1 missense variant T408A is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv), and ESM1b. The high‑accuracy AlphaMissense‑Optimized score is benign, while the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, a protein‑folding stability method, also predicts benign. Overall, the balance of evidence favors a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	Uncertain		1				-8.304	Likely Pathogenic	0.114	Likely Benign	Likely Benign	0.118	Likely Benign	0.37	Likely Benign	0.6	-0.06	Likely Benign	0.16	Likely Benign	0.72	Ambiguous	-3.07	Deleterious	0.540	Possibly Damaging	0.131	Benign	4.16	Benign	0.14	Tolerated			1	0	2.5	-30.03
c.1240A>G	M414V 2D AISynGAP1 M414V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; the remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. The SGM consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority. High‑accuracy assessments give AlphaMissense‑Optimized benign, SGM consensus pathogenic, and Foldetta uncertain. Because the high‑accuracy predictions are divided and the overall tool set is evenly split, there is no definitive evidence for pathogenicity or benignity. Thus, the variant is most likely inconclusive, and this lack of consensus does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	Uncertain		1				-8.003	Likely Pathogenic	0.541	Ambiguous	Likely Benign	0.261	Likely Benign	1.81	Ambiguous	0.4	1.73	Ambiguous	1.77	Ambiguous	0.95	Ambiguous	-2.95	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	3.43	Benign	0.24	Tolerated			2	1	2.3	-32.06
c.127G>A	G43S 2D AIThe SynGAP1 missense variant G43S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (6‑33423536‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same four high‑accuracy tools) also as benign; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, 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		Uncertain		2	6-33423536-G-A	1	6.20e-7	-3.301	Likely Benign	0.078	Likely Benign	Likely Benign	0.057	Likely Benign										-0.30	Neutral	0.162	Benign	0.096	Benign	4.29	Benign	0.00	Affected	4.32	1	1	0	-0.4	30.03
c.1339G>C	V447L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V447L is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Uncertain results are reported by FoldX, Rosetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Benign. Overall, the majority of evidence points to a benign effect, and this consensus does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1				-5.136	Likely Benign	0.491	Ambiguous	Likely Benign	0.180	Likely Benign	-1.13	Ambiguous	0.1	0.54	Ambiguous	-0.30	Likely Benign	0.03	Likely Benign	-0.29	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.61	Benign	0.90	Tolerated	3.37	32	1	2	-0.4	14.03
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	Uncertain		1	6-33438250-A-G	3	1.86e-6	-5.936	Likely Benign	0.071	Likely Benign	Likely Benign	0.116	Likely Benign	0.47	Likely Benign	0.0	0.55	Ambiguous	0.51	Ambiguous	0.85	Ambiguous	-2.32	Neutral	0.948	Possibly Damaging	0.124	Benign	3.35	Benign	0.13	Tolerated	3.37	32	0	1	0.4	-30.03
c.1352T>C	L451P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451P is reported in ClinVar as Pathogenic (ClinVar ID 3064222.0) and is not found in gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on these predictions, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Pathogenic		1				-14.549	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.750	Likely Pathogenic	6.92	Destabilizing	0.2	8.57	Destabilizing	7.75	Destabilizing	2.58	Destabilizing	-6.81	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.43	Pathogenic	0.00	Affected	3.37	34	-3	-3	-5.4	-16.04
c.1354G>A	V452I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V452I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT, while ESM1b also predicts pathogenicity. Uncertain predictions come from Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	Uncertain		1				-8.985	Likely Pathogenic	0.361	Ambiguous	Likely Benign	0.218	Likely Benign	-0.08	Likely Benign	0.1	0.51	Ambiguous	0.22	Likely Benign	0.25	Likely Benign	-0.99	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.26	Benign	0.05	Affected			4	3	0.3	14.03
c.1367A>C	Q456P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q456P is listed in ClinVar with an uncertain significance (ClinVar ID 2697090.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. High‑accuracy methods specifically report pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-15.250	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.469	Likely Benign	3.68	Destabilizing	0.2	8.43	Destabilizing	6.06	Destabilizing	0.82	Ambiguous	-5.66	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.34	Benign	0.07	Tolerated	3.37	34	-1	0	1.9	-31.01
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		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			1	-1	0.8	-10.04
c.1370G>A	S457N 2D AIThe SynGAP1 missense variant S457N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give a mixed picture: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the majority of individual predictors lean toward pathogenicity, but the high‑accuracy Foldetta result suggests a benign impact. Thus, the variant is most likely pathogenic based on the preponderance of predictions, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-10.221	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	0.241	Likely Benign	0.19	Likely Benign	0.0	-0.22	Likely Benign	-0.02	Likely Benign	0.67	Ambiguous	-2.76	Deleterious	0.940	Possibly Damaging	0.843	Possibly Damaging	3.28	Benign	0.06	Tolerated			1	1	-2.7	27.03
c.13C>G	R5G 2D AIThe SynGAP1 missense variant R5G is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as 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		Uncertain		1				-3.639	Likely Benign	0.150	Likely Benign	Likely Benign	0.169	Likely Benign										-0.16	Neutral	0.013	Benign	0.003	Benign	4.12	Benign	0.00	Affected	4.32	1	-2	-3	4.1	-99.14
c.1402A>G	M468V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from PROVEAN, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions are made by REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools, premPS and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments further clarify the variant’s impact: AlphaMissense‑Optimized predicts a benign effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also classifies the variant as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	Uncertain		1				-9.461	Likely Pathogenic	0.361	Ambiguous	Likely Benign	0.570	Likely Pathogenic	2.69	Destabilizing	0.1	2.20	Destabilizing	2.45	Destabilizing	0.89	Ambiguous	-1.66	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	-1.21	Pathogenic	0.08	Tolerated	3.37	31	1	2	2.3	-32.06
c.1404G>A	M468I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M468I is listed in ClinVar with an uncertain significance (ClinVar ID 3657719.0) and is present in gnomAD (6‑33438436‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and SIFT, while pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and Rosetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates a pathogenic impact for M468I, which does not contradict the ClinVar uncertain status but suggests a likely pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33438436-G-A	1	6.20e-7	-8.583	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.508	Likely Pathogenic	2.53	Destabilizing	0.2	1.89	Ambiguous	2.21	Destabilizing	0.37	Likely Benign	-1.06	Neutral	0.748	Possibly Damaging	0.886	Possibly Damaging	-1.10	Pathogenic	0.07	Tolerated	3.37	31	1	2	2.6	-18.03
c.1405G>A	A469T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A469T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and the Foldetta stability assessment (combining FoldX‑MD and Rosetta). The high‑accuracy subset shows AlphaMissense‑Optimized as benign, whereas SGM Consensus and Foldetta both predict pathogenic. Overall, the majority of evidence supports a pathogenic effect, and this conclusion does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-9.540	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.527	Likely Pathogenic	2.26	Destabilizing	0.1	1.90	Ambiguous	2.08	Destabilizing	0.34	Likely Benign	-1.46	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	-1.21	Pathogenic	0.42	Tolerated			1	0	-2.5	30.03
c.1408A>G	M470V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M470V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Consensus from most in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all score it as deleterious. Only two tools—SIFT and AlphaMissense‑Optimized—classify it as benign, while Rosetta and AlphaMissense‑Default remain inconclusive. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized reports a benign outcome, but the SGM‑Consensus (derived from a majority of pathogenic calls among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining pathogenic FoldX with uncertain Rosetta) both predict pathogenicity. Overall, the preponderance of evidence supports a likely pathogenic classification, which does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-8.856	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.770	Likely Pathogenic	2.73	Destabilizing	0.1	1.88	Ambiguous	2.31	Destabilizing	1.31	Destabilizing	-3.58	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.20	Pathogenic	0.15	Tolerated	3.37	34	1	2	2.3	-32.06
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		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	1	1	1.0	-28.06																10.1016/j.ajhg.2020.11.011
c.1417G>A	V473I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473I is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438449‑G‑A). Functional prediction tools that agree on benign impact include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions are provided by both polyPhen‑2 HumDiv and HumVar. Predictions that are inconclusive are AlphaMissense‑Default, ESM1b, Foldetta, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to no majority, and Foldetta is uncertain. Overall, the balance of evidence favors a benign effect for V473I, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	Uncertain		1	6-33438449-G-A	1	6.20e-7	-7.481	In-Between	0.418	Ambiguous	Likely Benign	0.203	Likely Benign	-0.12	Likely Benign	0.0	1.20	Ambiguous	0.54	Ambiguous	-0.06	Likely Benign	-0.91	Neutral	0.929	Possibly Damaging	0.917	Probably Damaging	3.74	Benign	0.18	Tolerated	3.37	34	3	4	0.3	14.03
c.1436G>A	R479Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R479Q is listed in ClinVar with an “Uncertain” significance and is present in gnomAD (variant ID 6‑33438468‑G‑A). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv and HumVar both predict a pathogenic impact. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also as likely benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect, and this consensus does not contradict the ClinVar “Uncertain” status; thus the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1	6-33438468-G-A	7	4.34e-6	-7.109	In-Between	0.259	Likely Benign	Likely Benign	0.191	Likely Benign	0.54	Ambiguous	0.1	0.57	Ambiguous	0.56	Ambiguous	0.49	Likely Benign	-1.16	Neutral	1.000	Probably Damaging	0.991	Probably Damaging	3.42	Benign	0.31	Tolerated	3.39	32	1	1	1.0	-28.06
c.1436G>C	R479P 2D 3DClick to see structure in 3D Viewer AIClinVar lists the SynGAP1 R479P variant as Uncertain, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Those that predict a pathogenic effect are FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are AlphaMissense‑Optimized and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as pathogenic. Overall, the majority of tools and the high‑accuracy methods support a pathogenic classification, which is in contrast to the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-11.795	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.277	Likely Benign	2.86	Destabilizing	0.2	3.88	Destabilizing	3.37	Destabilizing	0.81	Ambiguous	-3.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.18	Tolerated			0	-2	2.9	-59.07
c.1447A>G	I483V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions marked as uncertain include FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, whereas Foldetta remains uncertain. Overall, the balance of evidence from both general and high‑accuracy tools leans toward a benign effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	Conflicting		2				-10.121	Likely Pathogenic	0.523	Ambiguous	Likely Benign	0.228	Likely Benign	1.00	Ambiguous	0.0	0.27	Likely Benign	0.64	Ambiguous	1.02	Destabilizing	-0.86	Neutral	0.914	Possibly Damaging	0.921	Probably Damaging	3.23	Benign	0.03	Affected	3.37	32	3	4	-0.3	-14.03
c.1453C>A	R485S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R485S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FoldX, which scores 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 is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that return uncertain results are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for R485S, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-15.603	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.609	Likely Pathogenic	0.40	Likely Benign	0.1	1.07	Ambiguous	0.74	Ambiguous	0.82	Ambiguous	-5.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.93	Pathogenic	0.00	Affected			0	-1	3.7	-69.11
c.1454G>A	R485H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R485H missense variant is listed in ClinVar as Benign (ClinVar ID 3707943.0) and is present in the gnomAD database (gnomAD ID 6‑33438486‑G‑A). Functional prediction tools that agree on a benign effect are Rosetta and Foldetta, while the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Benign		1	6-33438486-G-A	13	8.05e-6	-13.628	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.618	Likely Pathogenic	0.77	Ambiguous	0.1	0.12	Likely Benign	0.45	Likely Benign	1.13	Destabilizing	-4.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.93	Pathogenic	0.00	Affected	3.37	35	0	2	1.3	-19.05
c.1463C>T	T488M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T488M is listed in ClinVar with an uncertain significance (ClinVar ID 2824521.0) and is present in gnomAD (ID 6‑33438495‑C‑T). Prediction tools that indicate a benign effect include premPS and FATHMM, whereas the majority of algorithms predict a pathogenic outcome: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as inconclusive. No other tools provide definitive evidence. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33438495-C-T	2	1.24e-6	-12.459	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.746	Likely Pathogenic	0.66	Ambiguous	0.3	1.62	Ambiguous	1.14	Ambiguous	0.46	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.21	Benign	0.00	Affected	3.37	35	-1	-1	2.6	30.09
c.1468G>C	A490P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Among the available in‑silico predictors, 10 tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) uniformly predict a pathogenic effect, whereas only Foldetta predicts a benign outcome; FoldX, Rosetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) is benign. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-12.905	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	0.878	Likely Pathogenic	-1.27	Ambiguous	0.1	1.31	Ambiguous	0.02	Likely Benign	1.07	Destabilizing	-4.81	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.01	Affected	3.37	35	-1	1	-3.4	26.04
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	Conflicting		2				-16.175	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.510	Likely Pathogenic	1.53	Ambiguous	0.1	1.90	Ambiguous	1.72	Ambiguous	1.42	Destabilizing	-3.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.99	Benign	0.01	Affected	3.37	35	1	0	0.4	0.94
c.1483G>A	E495K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495K is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include FoldX and Foldetta, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools with inconclusive results (Rosetta and premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus also as pathogenic, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) indicates a benign effect. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for E495K, which is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-11.478	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.869	Likely Pathogenic	0.15	Likely Benign	0.2	0.66	Ambiguous	0.41	Likely Benign	0.70	Ambiguous	-3.91	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.29	Pathogenic	0.01	Affected	3.37	35	1	0	-0.4	-0.94
c.1484A>G	E495G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E495G missense variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438516‑A‑G). Among the available in‑silico predictors, the following tools uniformly indicate a pathogenic effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which itself is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a benign outcome; predictions that are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta as “Uncertain.” Overall, the preponderance of pathogenic predictions strongly suggests that the variant is most likely pathogenic, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33438516-A-G	1	6.20e-7	-9.400	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	0.867	Likely Pathogenic	1.21	Ambiguous	0.0	2.06	Destabilizing	1.64	Ambiguous	0.78	Ambiguous	-6.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.46	Pathogenic	0.02	Affected	3.37	35	-2	0	3.1	-72.06
c.1493T>G	M498R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498R is listed in ClinVar as Pathogenic (ClinVar ID 3907767.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only polyPhen‑2 HumVar; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Pathogenic		1				-8.812	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.869	Likely Pathogenic	3.85	Destabilizing	0.2	2.35	Destabilizing	3.10	Destabilizing	1.76	Destabilizing	-4.53	Deleterious	0.464	Possibly Damaging	0.120	Benign	-1.36	Pathogenic	0.00	Affected			0	-1	-6.4	24.99
c.1499T>C	L500P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500P is listed in ClinVar (ID 2708686.0) as Pathogenic and is not reported in gnomAD. All available in‑silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Pathogenic		1				-15.898	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.894	Likely Pathogenic	5.91	Destabilizing	0.3	8.90	Destabilizing	7.41	Destabilizing	1.92	Destabilizing	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.37	Pathogenic	0.01	Affected	3.37	35	-3	-3	-5.4	-16.04
c.1511A>G	K504R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438543‑A‑G). Consensus from most in‑silico predictors is benign: REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a benign effect, while only FATHMM predicts pathogenicity. Uncertain calls come from Rosetta and premPS. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the preponderance of evidence indicates the variant is most likely benign, 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	Uncertain		1	6-33438543-A-G	2	1.24e-6	-4.365	Likely Benign	0.088	Likely Benign	Likely Benign	0.238	Likely Benign	0.13	Likely Benign	0.1	0.51	Ambiguous	0.32	Likely Benign	0.94	Ambiguous	-2.16	Neutral	0.002	Benign	0.015	Benign	-1.41	Pathogenic	0.11	Tolerated	3.37	35	2	3	-0.6	28.01
c.1513T>C	Y505H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505H is listed in ClinVar as Pathogenic (ClinVar ID 3064218.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also Pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among predictive tools, the variant is most likely pathogenic, consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Pathogenic		1				-11.383	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.646	Likely Pathogenic	2.91	Destabilizing	0.1	2.88	Destabilizing	2.90	Destabilizing	1.60	Destabilizing	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.64	Benign	0.00	Affected	3.37	35	2	0	-1.9	-26.03
c.1513T>G	Y505D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505D is listed in ClinVar as Pathogenic (ClinVar ID 3172759.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect are limited to FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized scores the variant as Pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as Pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Pathogenic		1				-14.078	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.718	Likely Pathogenic	4.98	Destabilizing	0.1	4.72	Destabilizing	4.85	Destabilizing	2.49	Destabilizing	-9.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.60	Benign	0.00	Affected	3.37	35	-3	-4	-2.2	-48.09
c.1516C>T	L506F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; premPS and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-11.262	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	0.464	Likely Benign	4.92	Destabilizing	0.8	5.76	Destabilizing	5.34	Destabilizing	0.91	Ambiguous	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.01	Affected	3.37	35	0	2	-1.0	34.02
c.1540A>T	I514F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report it as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, classifies the variant as pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-13.383	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.601	Likely Pathogenic	2.35	Destabilizing	0.3	3.74	Destabilizing	3.05	Destabilizing	0.93	Ambiguous	-3.98	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	2.89	Benign	0.00	Affected	3.37	35	0	1	-1.7	34.02
c.1552T>C	Y518H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y518H, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-9.797	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.496	Likely Benign	2.39	Destabilizing	0.4	0.82	Ambiguous	1.61	Ambiguous	1.31	Destabilizing	-4.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.08	Tolerated			0	2	-1.9	-26.03
c.1558T>C	S520P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520P 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, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while premPS remains inconclusive. 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, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. Overall, the evidence strongly supports a pathogenic impact for S520P, 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 Pathogenic	GAP	Uncertain		1				-12.707	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.855	Likely Pathogenic	3.72	Destabilizing	0.8	8.86	Destabilizing	6.29	Destabilizing	0.83	Ambiguous	-4.57	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	-1.32	Pathogenic	0.01	Affected			1	-1	-0.8	10.04
c.1559C>T	S520F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include Rosetta, Foldetta, and premPS. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX gives an uncertain result. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-12.541	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.833	Likely Pathogenic	-1.20	Ambiguous	0.4	0.39	Likely Benign	-0.41	Likely Benign	0.25	Likely Benign	-5.57	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.36	Pathogenic	0.00	Affected	3.37	35	-2	-3	3.6	60.10
c.155C>T	S52L 2D AISynGAP1 missense variant S52L is listed in ClinVar with an uncertain significance and is present in the gnomAD database (ID 6‑33423564‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: 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. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the collective evidence points to a likely benign effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1	6-33423564-C-T	1	6.20e-7	-7.199	In-Between	0.688	Likely Pathogenic	Likely Benign	0.087	Likely Benign										-1.41	Neutral	0.829	Possibly Damaging	0.706	Possibly Damaging	4.10	Benign	0.00	Affected	4.32	1	-3	-2	4.6	26.08
c.1600T>C	S534P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438843‑T‑C). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy assessments are consistent with a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the aggregate predictions, the variant is most likely benign, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1	6-33438843-T-C	3	1.86e-6	-5.056	Likely Benign	0.265	Likely Benign	Likely Benign	0.203	Likely Benign	-0.40	Likely Benign	0.2	0.35	Likely Benign	-0.03	Likely Benign	0.47	Likely Benign	-3.81	Deleterious	0.993	Probably Damaging	0.993	Probably Damaging	3.32	Benign	0.05	Affected	3.37	35	-1	1	-0.8	10.04
c.1631G>A	R544Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R544Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438874‑G‑A). Prediction tools that classify the change as benign include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is not contradictory to the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33438874-G-A	1	6.20e-7	-10.281	Likely Pathogenic	0.596	Likely Pathogenic	Likely Benign	0.542	Likely Pathogenic	0.19	Likely Benign	0.2	0.87	Ambiguous	0.53	Ambiguous	1.40	Destabilizing	-2.41	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.09	Tolerated	3.37	35	1	1	1.0	-28.06
c.1635G>A	M545I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545I is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions arise from FoldX, Rosetta, and SIFT, whereas pathogenic predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; premPS remains inconclusive. High‑accuracy methods provide mixed evidence: AlphaMissense‑Optimized indicates pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also suggests likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the preponderance of conventional tools and the SGM Consensus lean toward pathogenicity, whereas the Foldetta result is an outlier. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict its ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-8.348	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.592	Likely Pathogenic	0.47	Likely Benign	0.1	0.14	Likely Benign	0.31	Likely Benign	0.63	Ambiguous	-3.61	Deleterious	0.935	Possibly Damaging	0.941	Probably Damaging	-1.27	Pathogenic	0.28	Tolerated	3.37	35	1	2	2.6	-18.03
c.163C>A	Q55K 2D AIThe SynGAP1 missense variant Q55K is listed in ClinVar (ID 520688.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33423572‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		2	6-33423572-C-A	24	1.49e-5	-5.840	Likely Benign	0.612	Likely Pathogenic	Likely Benign	0.085	Likely Benign										-1.21	Neutral	0.140	Benign	0.184	Benign	3.91	Benign	0.00	Affected	4.32	1	1	1	-0.4	0.04
c.1663G>A	V555I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V555I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, Rosetta, 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, while FoldX, 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	Uncertain		1				-4.544	Likely Benign	0.084	Likely Benign	Likely Benign	0.253	Likely Benign	-0.82	Ambiguous	0.0	-0.41	Likely Benign	-0.62	Ambiguous	-0.55	Ambiguous	0.45	Neutral	0.002	Benign	0.002	Benign	-1.26	Pathogenic	1.00	Tolerated			4	3	0.3	14.03
c.1667A>T	N556I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556I is catalogued in ClinVar as benign (ClinVar ID 2692844.0) and is observed in gnomAD (ID 6‑33438910‑A‑T). Functional prediction tools cluster into two groups: benign predictions come from Rosetta, Foldetta, and premPS, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Two tools report uncertainty: FoldX 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 (integrating FoldX‑MD and Rosetta outputs) as benign. Taken together, the majority of predictions favor a pathogenic effect, whereas the ClinVar annotation indicates benign. Thus, the computational evidence contradicts the ClinVar status, suggesting 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	Likely Benign		1	6-33438910-A-T			-13.391	Likely Pathogenic	0.929	Likely Pathogenic	Ambiguous	0.761	Likely Pathogenic	0.64	Ambiguous	0.0	0.17	Likely Benign	0.41	Likely Benign	0.26	Likely Benign	-7.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.35	Pathogenic	0.02	Affected	3.37	35	-3	-2	8.0	-0.94
c.1673A>G	H558R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H558R is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from AlphaMissense‑Optimized, Rosetta, SIFT, and polyPhen‑2 HumVar, while pathogenic predictions arise from REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Four tools give inconclusive results: AlphaMissense‑Default, SGM‑Consensus, FoldX, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, 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	Uncertain		1				-14.445	Likely Pathogenic	0.554	Ambiguous	Likely Benign	0.587	Likely Pathogenic	-1.14	Ambiguous	0.1	-0.23	Likely Benign	-0.69	Ambiguous	1.03	Destabilizing	-4.94	Deleterious	0.677	Possibly Damaging	0.239	Benign	-1.24	Pathogenic	0.14	Tolerated	3.37	35	0	2	-1.3	19.05
c.169C>T	L57F 2D AIThe SynGAP1 missense variant L57F (ClinVar ID 1973575.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. 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. This conclusion aligns with the ClinVar “Uncertain” status, as it does not contradict the current classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		2				-5.096	Likely Benign	0.459	Ambiguous	Likely Benign	0.051	Likely Benign										-0.78	Neutral	0.824	Possibly Damaging	0.879	Possibly Damaging	3.96	Benign	0.00	Affected	4.32	1	2	0	-1.0	34.02
c.1702G>T	V568L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568L is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Among the available in‑silico predictors, eight tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic effect, whereas three tools (FoldX, Foldetta, and polyPhen‑2 HumVar) predict a benign outcome; the remaining three (Rosetta, premPS, AlphaMissense‑Optimized) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. Overall, the preponderance of evidence points to a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-9.503	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	0.651	Likely Pathogenic	-0.30	Likely Benign	0.3	0.57	Ambiguous	0.14	Likely Benign	0.56	Ambiguous	-2.69	Deleterious	0.511	Possibly Damaging	0.147	Benign	-1.23	Pathogenic	0.04	Affected	3.37	35	1	2	-0.4	14.03
c.1712C>T	S571L 2D 3DClick to see structure in 3D Viewer AISynGAP1 S571L is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33440764‑C‑T). Prediction tools cluster into two groups: benign predictions come from premPS and AlphaMissense‑Optimized, while the remaining nine tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—indicate pathogenicity. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic (a majority vote of pathogenic predictions from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain due to conflicting FoldX‑MD and Rosetta outputs. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33440764-C-T	1	6.23e-7	-11.651	Likely Pathogenic	0.660	Likely Pathogenic	Likely Benign	0.841	Likely Pathogenic	-1.53	Ambiguous	0.1	-1.05	Ambiguous	-1.29	Ambiguous	0.27	Likely Benign	-5.61	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	-1.25	Pathogenic	0.04	Affected	3.37	35	-2	-3	4.6	26.08
c.1726T>C	C576R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C576R is listed in ClinVar with an uncertain significance (ClinVar ID 2780076.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it pathogenic, the SGM‑Consensus (derived from the majority of high‑confidence predictors) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the overwhelming majority of computational evidence indicates that C576R is likely pathogenic, a conclusion that is consistent with, but not in conflict with, the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Conflicting		2				-14.886	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.579	Likely Pathogenic	7.20	Destabilizing	1.0	4.09	Destabilizing	5.65	Destabilizing	1.64	Destabilizing	-10.88	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected	3.37	35	-3	-4	-7.0	53.05
c.172A>G	M58V 2D AIThe SynGAP1 missense variant M58V is listed in ClinVar (ID 2962156.0) with an uncertain significance status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus from AlphaMissense‑Optimized, SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (protein‑folding stability) is available only for the first two; Foldetta data are missing. The SGM Consensus, based on a majority of benign predictions, indicates a likely benign outcome. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-2.211	Likely Benign	0.688	Likely Pathogenic	Likely Benign	0.160	Likely Benign										-0.71	Neutral	0.006	Benign	0.091	Benign	4.19	Benign	0.00	Affected	4.32	1	1	2	2.3	-32.06
c.1736G>A	R579Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R579Q is listed in ClinVar with an uncertain significance (ClinVar ID 3964539.0) and is present in gnomAD (variant ID 6‑33440788‑G‑A). Prediction tools that classify the variant as benign include SIFT and AlphaMissense‑Optimized, whereas the majority of other in‑silico predictors (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign effect, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an inconclusive result. FoldX and Rosetta individually report uncertain effects. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that R579Q is most likely pathogenic, which is consistent with its ClinVar status of uncertain significance rather than a benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1	6-33440788-G-A	18	1.12e-5	-9.193	Likely Pathogenic	0.690	Likely Pathogenic	Likely Benign	0.673	Likely Pathogenic	0.65	Ambiguous	0.1	0.70	Ambiguous	0.68	Ambiguous	1.13	Destabilizing	-3.31	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.34	Pathogenic	0.06	Tolerated	3.37	34	1	1	1.0	-28.06
c.1763T>C	L588P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy 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 calculations, is pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-14.771	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.932	Likely Pathogenic	5.61	Destabilizing	0.5	12.91	Destabilizing	9.26	Destabilizing	2.33	Destabilizing	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.42	Pathogenic	0.00	Affected	3.38	34	-3	-3	-5.4	-16.04
c.1778T>C	L593P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L593P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic outcome. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, a conclusion that contradicts its current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-13.961	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.777	Likely Pathogenic	5.75	Destabilizing	0.9	10.77	Destabilizing	8.26	Destabilizing	2.43	Destabilizing	-6.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.77	Benign	0.00	Affected			-3	-3	-5.4	-16.04
c.1784T>A	L595Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L595Q is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized—predict a pathogenic effect, and the SGM‑Consensus score indicates a likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized returns a pathogenic prediction, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a likely pathogenic result, while Foldetta’s stability analysis is inconclusive. Overall, the majority of computational evidence points to a pathogenic effect, which does not contradict the ClinVar designation of uncertain significance but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-15.101	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.733	Likely Pathogenic	0.79	Ambiguous	0.1	1.40	Ambiguous	1.10	Ambiguous	1.99	Destabilizing	-5.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.75	Benign	0.00	Affected	3.37	35	-2	-2	-7.3	14.97
c.1784T>C	L595P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595P is listed in ClinVar with an “Uncertain” status (ClinVar ID 3172762.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-11.856	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.747	Likely Pathogenic	2.09	Destabilizing	0.8	5.88	Destabilizing	3.99	Destabilizing	1.78	Destabilizing	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.72	Benign	0.00	Affected	3.37	35	-3	-3	-5.4	-16.04
c.1789T>C	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is listed in ClinVar with an uncertain significance (ClinVar ID 3658115.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. The high‑accuracy AlphaMissense‑Optimized score is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for F597L, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.929	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			2	0	1.0	-34.02
c.182A>C	E61A 2D AIThe SynGAP1 missense variant E61A is listed in ClinVar (ID 3767543.0) 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‑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 remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-5.235	Likely Benign	0.453	Ambiguous	Likely Benign	0.074	Likely Benign										-1.52	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	4.12	Benign	0.00	Affected			0	-1	5.3	-58.04
c.1832T>C	M611T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M611T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33440884‑T‑C). 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. Four tools (FoldX, Rosetta, Foldetta, premPS) return uncertain or inconclusive results. 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 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	GAP	Uncertain		1	6-33440884-T-C	1	6.19e-7	-5.696	Likely Benign	0.101	Likely Benign	Likely Benign	0.240	Likely Benign	1.98	Ambiguous	0.2	0.94	Ambiguous	1.46	Ambiguous	0.87	Ambiguous	-2.40	Neutral	0.034	Benign	0.038	Benign	-1.19	Pathogenic	0.29	Tolerated	3.37	35	-1	-1	-2.6	-30.09
c.1835A>C	Q612P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q612P is listed in ClinVar (ID 3660462.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, PROVEAN, and the SGM Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). The high‑accuracy AlphaMissense‑Optimized predicts benign, whereas the SGM Consensus predicts likely pathogenic; Foldetta, a folding‑stability method combining FoldX‑MD and Rosetta outputs, returns an uncertain result and is therefore not factored into the consensus. Overall, the majority of evidence supports a pathogenic effect, which contrasts with the ClinVar uncertain classification. Thus, based on current predictions, 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	GAP	Uncertain		1				-9.684	Likely Pathogenic	0.673	Likely Pathogenic	Likely Benign	0.671	Likely Pathogenic	-0.19	Likely Benign	0.3	3.06	Destabilizing	1.44	Ambiguous	0.56	Ambiguous	-5.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.31	Pathogenic	0.19	Tolerated			0	-1	1.9	-31.01
c.1851G>T	E617D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617D is listed in ClinVar with an uncertain significance (ID 2584916.0) and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign or likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact, while Rosetta remains inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the preponderance of evidence supports a benign classification, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1				-1.349	Likely Benign	0.241	Likely Benign	Likely Benign	0.322	Likely Benign	0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	2	3	0.0	-14.03
c.1855A>T	T619S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T619S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign outcome, whereas the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result. Overall, the majority of evidence points to a pathogenic effect for T619S, and this conclusion does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-8.608	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	0.602	Likely Pathogenic	1.09	Ambiguous	0.2	1.35	Ambiguous	1.22	Ambiguous	0.85	Ambiguous	-3.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.05	Affected	3.37	35	1	1	-0.1	-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	Uncertain		1				-11.319	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	0.480	Likely Benign	1.80	Ambiguous	0.7	1.69	Ambiguous	1.75	Ambiguous	1.42	Destabilizing	-2.96	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.07	Benign	0.01	Affected			2	1	0.4	-14.03
c.1877T>C	I626T 2D AISynGAP1 missense variant I626T is listed in ClinVar with an uncertain significance (ClinVar ID 3359331.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the consensus of the majority of tools points to a pathogenic effect, contradicting the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-10.420	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.640	Likely Pathogenic	2.94	Destabilizing	0.1	2.70	Destabilizing	2.82	Destabilizing	2.23	Destabilizing	-4.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.04	Benign	0.00	Affected			0	-1	-5.2	-12.05
c.187G>A	E63K 2D AIThe SynGAP1 E63K missense variant (ClinVar ID 2830630.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict a pathogenic outcome. AlphaMissense‑Optimized is inconclusive, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. Overall, the high‑accuracy consensus leans toward a benign effect, and this assessment does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-4.976	Likely Benign	0.894	Likely Pathogenic	Ambiguous	0.103	Likely Benign										-0.70	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	1	0	-0.4	-0.94
c.187G>C	E63Q 2D AIThe SynGAP1 missense variant E63Q is listed in ClinVar (ID 2132335.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions 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		Uncertain		1				-4.038	Likely Benign	0.687	Likely Pathogenic	Likely Benign	0.078	Likely Benign										-0.85	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	3.90	Benign	0.00	Affected	4.32	1	2	2	0.0	-0.98
c.1913A>G	K638R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PROVEAN and polyPhen‑2 HumDiv predict a pathogenic impact, while premPS remains inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is benign. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1				-2.700	Likely Benign	0.110	Likely Benign	Likely Benign	0.216	Likely Benign	0.09	Likely Benign	0.1	-0.04	Likely Benign	0.03	Likely Benign	0.53	Ambiguous	-2.55	Deleterious	0.649	Possibly Damaging	0.240	Benign	3.41	Benign	0.13	Tolerated	3.37	31	2	3	-0.6	28.01
c.1918A>T	T640S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640S is listed in ClinVar as Benign (ClinVar ID 2980241.0) and is present in the gnomAD database (gnomAD ID 6‑33441177‑A‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive result is from FoldX, which is treated as unavailable. High‑accuracy assessments confirm benignity: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Overall, the variant is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Benign		1	6-33441177-A-T	1	6.20e-7	-2.371	Likely Benign	0.062	Likely Benign	Likely Benign	0.088	Likely Benign	-0.78	Ambiguous	0.1	0.43	Likely Benign	-0.18	Likely Benign	-0.30	Likely Benign	0.92	Neutral	0.000	Benign	0.001	Benign	3.60	Benign	0.33	Tolerated	3.37	30	1	1	-0.1	-14.03
c.1942T>C	F648L 2D AISynGAP1 missense variant F648L is listed in ClinVar with an uncertain significance (ClinVar ID 3383902.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b—consistently predict pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic change. Taken together, the preponderance of evidence points to a pathogenic impact for F648L, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.468	Likely Benign	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			2	0	1.0	-34.02
c.194A>G	H65R 2D AIThe SynGAP1 missense variant H65R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33425802‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33425802-A-G	1	6.20e-7	-1.980	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic	0.073	Likely Benign										-1.60	Neutral	0.462	Possibly Damaging	0.227	Benign	4.19	Benign	0.00	Affected	4.32	1	2	0	-1.3	19.05
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	Uncertain		1				-7.050	In-Between	0.301	Likely Benign	Likely Benign	0.146	Likely Benign	3.28	Destabilizing	0.3	2.18	Destabilizing	2.73	Destabilizing	1.32	Destabilizing	-2.25	Neutral	0.227	Benign	0.039	Benign	3.28	Benign	0.08	Tolerated			2	1	0.4	-14.03
c.196C>G	P66A 2D AIThe SynGAP1 P66A missense variant (ClinVar ID 1303518.0) is listed as “Uncertain” and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. Separately, the high‑accuracy AlphaMissense‑Optimized result is “Uncertain,” the SGM‑Consensus remains “Likely Benign,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the predictions are mixed, but the majority of high‑confidence tools lean toward a benign effect. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-2.845	Likely Benign	0.891	Likely Pathogenic	Ambiguous	0.091	Likely Benign										-1.56	Neutral	0.805	Possibly Damaging	0.539	Possibly Damaging	4.04	Benign	0.00	Affected	4.32	1	1	-1	3.4	-26.04
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		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	1	-1	0.8	-10.04
c.1970G>T	W657L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant W657L is listed in ClinVar with an uncertain significance (ClinVar ID 2767440.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta predicts a benign folding‑stability change. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the ClinVar uncertain status but leans toward pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-14.411	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.213	Likely Benign	0.14	Likely Benign	0.1	0.73	Ambiguous	0.44	Likely Benign	0.87	Ambiguous	-10.86	Deleterious	0.277	Benign	0.078	Benign	3.52	Benign	0.14	Tolerated	3.39	24	-2	-2	4.7	-73.05
c.1971G>C	W657C 2D AISynGAP1 missense variant W657C is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL and FATHMM. Those that predict a deleterious effect are FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta reports an uncertain outcome. High‑accuracy assessments further support a damaging interpretation: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that W657C is most likely pathogenic, which does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-12.035	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.463	Likely Benign	2.74	Destabilizing	0.3	1.69	Ambiguous	2.22	Destabilizing	1.30	Destabilizing	-11.06	Deleterious	1.000	Probably Damaging	0.982	Probably Damaging	3.43	Benign	0.03	Affected			-8	-2	3.4	-83.07
c.2029A>T	S677C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677C is reported in ClinVar as Benign (ClinVar ID 2825814.0) and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, SIFT, and ESM1b predict a pathogenic impact. High‑accuracy predictors all support a benign outcome: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding‑stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Benign		1				-8.496	Likely Pathogenic	0.076	Likely Benign	Likely Benign	0.153	Likely Benign	-0.51	Ambiguous	0.3	-0.30	Likely Benign	-0.41	Likely Benign	0.15	Likely Benign	-2.41	Neutral	0.932	Possibly Damaging	0.222	Benign	3.25	Benign	0.04	Affected	3.41	23	-1	0	3.3	16.06
c.2050G>A	D684N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684N is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus also reports it as likely pathogenic, and the Foldetta stability analysis is inconclusive. Protein‑stability predictors FoldX and Rosetta likewise return uncertain results. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the current ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-13.155	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.382	Likely Benign	1.47	Ambiguous	0.8	1.76	Ambiguous	1.62	Ambiguous	0.37	Likely Benign	-4.99	Deleterious	0.999	Probably Damaging	0.746	Possibly Damaging	3.39	Benign	0.01	Affected			2	1	0.0	-0.98
c.2050G>C	D684H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive or missing. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Uncertain		1				-14.194	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.613	Likely Pathogenic	3.36	Destabilizing	1.0	2.95	Destabilizing	3.16	Destabilizing	0.55	Ambiguous	-6.98	Deleterious	1.000	Probably Damaging	0.972	Probably Damaging	3.36	Benign	0.00	Affected	3.42	17	-1	1	0.3	22.05
c.2060G>A	R687Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687Q is annotated in ClinVar as benign (ClinVar ID 2693600.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, SGM‑Consensus indicating pathogenicity, and Foldetta (integrating FoldX‑MD and Rosetta outputs) classifying it as benign. With three high‑accuracy tools giving benign or uncertain results and only one (SGM‑Consensus) suggesting pathogenicity, the overall evidence leans toward a benign effect. This prediction aligns with the ClinVar benign classification, indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Benign		1				-10.002	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.401	Likely Benign	0.92	Ambiguous	0.1	-0.37	Likely Benign	0.28	Likely Benign	1.55	Destabilizing	-3.37	Deleterious	1.000	Probably Damaging	0.844	Possibly Damaging	3.91	Benign	0.03	Affected	3.42	17	1	1	1.0	-28.06
c.2075T>A	L692Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692Q is listed in ClinVar as Pathogenic (ClinVar ID 2714634.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Pathogenic		1				-13.873	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.596	Likely Pathogenic	3.24	Destabilizing	0.1	3.27	Destabilizing	3.26	Destabilizing	2.76	Destabilizing	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.06	Benign	0.00	Affected	3.42	17	-2	-2	-7.3	14.97
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	Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	0.351	Likely Benign	2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	1	2	0.4	-14.03
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	Uncertain		1	6-33441360-C-T	3	1.86e-6	-4.375	Likely Benign	0.221	Likely Benign	Likely Benign	0.132	Likely Benign	1.33	Ambiguous	0.0	0.12	Likely Benign	0.73	Ambiguous	-0.36	Likely Benign	0.78	Neutral	0.044	Benign	0.025	Benign	3.48	Benign	1.00	Tolerated	3.47	10	-1	1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
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	Uncertain		1	6-33441372-A-C	1	6.20e-7	-5.787	Likely Benign	0.436	Ambiguous	Likely Benign	0.142	Likely Benign	-0.10	Likely Benign	0.0	0.33	Likely Benign	0.12	Likely Benign	-0.02	Likely Benign	-0.24	Neutral	0.997	Probably Damaging	0.969	Probably Damaging	3.42	Benign	0.78	Tolerated	3.47	10	1	1	0.4	-0.04
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	Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	0.170	Likely Benign	3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	1	2	0.4	-14.03
c.2158G>A	D720N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D720N is listed in ClinVar as benign (ClinVar ID 2837618.0) and is present in gnomAD (ID 6‑33441623‑G‑A). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus as pathogenic. With seven pathogenic versus six benign predictions overall, the variant is most likely pathogenic according to in‑silico evidence, which contradicts the benign classification in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	Likely Benign		1	6-33441623-G-A	5	3.10e-6	-9.135	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	0.289	Likely Benign	0.01	Likely Benign	0.0	-0.20	Likely Benign	-0.10	Likely Benign	0.46	Likely Benign	-3.74	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.18	Pathogenic	0.01	Affected	3.50	9	1	2	0.0	-0.98
c.2186A>G	N729S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus also as benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	Uncertain		1				-1.578	Likely Benign	0.066	Likely Benign	Likely Benign	0.063	Likely Benign	0.14	Likely Benign	0.1	1.34	Ambiguous	0.74	Ambiguous	-0.36	Likely Benign	-0.42	Neutral	0.221	Benign	0.027	Benign	3.38	Benign	0.93	Tolerated	3.59	7	1	1	2.7	-27.03
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		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	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		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	3	2	0.6	-28.01
c.2195G>C	R732T 2D AISynGAP1 missense variant R732T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b). AlphaMissense‑Default remains uncertain. The high‑accuracy AlphaMissense‑Optimized predicts a benign effect, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors a benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact, which does not contradict the current ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1				-8.545	Likely Pathogenic	0.434	Ambiguous	Likely Benign	0.075	Likely Benign										-1.96	Neutral	0.999	Probably Damaging	0.892	Possibly Damaging	2.59	Benign	0.12	Tolerated	3.59	7	-1	-1	3.8	-55.08
c.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		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	1	-1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2206C>T	R736C 2D AISynGAP1 missense variant R736C is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441671‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates a benign effect, which does not conflict with the ClinVar uncertain designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Conflicting		3	6-33441671-C-T	8	4.96e-6	-7.113	In-Between	0.120	Likely Benign	Likely Benign	0.190	Likely Benign										-2.06	Neutral	0.999	Probably Damaging	0.825	Possibly Damaging	2.48	Pathogenic	0.00	Affected	4.07	3	-4	-3	7.0	-53.05
c.2207G>A	R736H 2D AIThe SynGAP1 missense variant R736H is listed in ClinVar (ID 1351080.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441672‑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 show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign. Foldetta results are not available. Overall, the majority of computational evidence indicates a benign impact, and this does not contradict the ClinVar “Uncertain” 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.	Likely Benign		Uncertain		1	6-33441672-G-A	6	3.72e-6	-5.409	Likely Benign	0.067	Likely Benign	Likely Benign	0.029	Likely Benign										-0.12	Neutral	0.004	Benign	0.001	Benign	2.50	Benign	0.00	Affected	4.07	3	2	0	1.3	-19.05
c.2210A>C	Q737P 2D AIThe SynGAP1 missense variant Q737P is listed in ClinVar (ID 2580571.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Taken together, the preponderance of evidence supports a benign classification for Q737P, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-2.407	Likely Benign	0.054	Likely Benign	Likely Benign	0.154	Likely Benign										-1.22	Neutral	0.005	Benign	0.013	Benign	2.78	Benign	0.04	Affected	4.07	3	-1	0	1.9	-31.01
c.2214T>G	S738R 2D AIThe SynGAP1 missense variant S738R is listed in ClinVar (ID 1592652.0) as Benign and is present in gnomAD (variant ID 6‑33441679‑T‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar designation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1	6-33441679-T-G	1	6.20e-7	-4.241	Likely Benign	0.570	Likely Pathogenic	Likely Benign	0.068	Likely Benign										-1.55	Neutral	0.473	Possibly Damaging	0.193	Benign	2.69	Benign	0.01	Affected	4.32	2	0	-1	-3.7	69.11
c.2215G>C	E739Q 2D AIThe SynGAP1 missense variant E739Q is listed in ClinVar (ID 2429558.0) with an “Uncertain” status and is not reported in 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-2.846	Likely Benign	0.161	Likely Benign	Likely Benign	0.071	Likely Benign										-1.06	Neutral	0.801	Possibly Damaging	0.339	Benign	2.57	Benign	0.00	Affected	4.32	2	2	2	0.0	-0.98
c.2216A>T	E739V 2D AIThe SynGAP1 missense variant E739V 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM 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 preponderance of evidence from both general and high‑accuracy predictors points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-3.136	Likely Benign	0.274	Likely Benign	Likely Benign	0.085	Likely Benign										-1.86	Neutral	0.891	Possibly Damaging	0.575	Possibly Damaging	2.47	Pathogenic	0.00	Affected	4.32	2	-2	-2	7.7	-29.98
c.2217G>C	E739D 2D AIThe SynGAP1 missense variant E739D is listed in ClinVar (ID 3661302.0) 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). Only SIFT predicts a pathogenic outcome. 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 majority of evidence points to a benign effect, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-3.369	Likely Benign	0.062	Likely Benign	Likely Benign	0.097	Likely Benign										-0.49	Neutral	0.002	Benign	0.005	Benign	2.59	Benign	0.00	Affected			3	2	0.0	-14.03
c.2218C>T	R740W 2D AIThe SynGAP1 missense variant R740W is listed in ClinVar with an uncertain significance and is present in the gnomAD database (ID 6‑33441683‑C‑T). Prediction tools that classify the variant as benign include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized predicting a benign effect; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two benign vs. two pathogenic calls) and is treated as unavailable, and no Foldetta stability data are reported. Overall, the majority of conventional tools (five pathogenic vs. four benign) suggest a pathogenic impact, whereas the single high‑accuracy tool indicates benign. Thus, the variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict the ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		2	6-33441683-C-T	6	3.72e-6	-8.561	Likely Pathogenic	0.168	Likely Benign	Likely Benign	0.180	Likely Benign										-3.09	Deleterious	1.000	Probably Damaging	0.938	Probably Damaging	2.52	Benign	0.01	Affected	4.32	2	2	-3	3.6	30.03
c.2219G>A	R740Q 2D AIThe SynGAP1 missense variant R740Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441684‑G‑A). Functional 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 outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so it does not influence the assessment. Overall, the majority of predictions indicate that R740Q is most likely benign, which is consistent with the ClinVar “Uncertain” classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33441684-G-A	4	2.48e-6	-5.195	Likely Benign	0.078	Likely Benign	Likely Benign	0.102	Likely Benign										-0.67	Neutral	0.999	Probably Damaging	0.881	Possibly Damaging	2.60	Benign	0.08	Tolerated	4.32	2	1	1	1.0	-28.06
c.221G>A	S74N 2D AIThe SynGAP1 missense variant S74N is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33425829‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability result is available. Overall, the majority of computational evidence indicates that the variant is most likely benign, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33425829-G-A	5	3.10e-6	-5.156	Likely Benign	0.112	Likely Benign	Likely Benign	0.031	Likely Benign										-0.89	Neutral	0.043	Benign	0.007	Benign	4.09	Benign	0.00	Affected	4.32	1	1	1	-2.7	27.03
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		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	1	-1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2224C>T	R742W 2D AIThe SynGAP1 missense variant R742W is listed in ClinVar (ID 2581888.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441689‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, which is consistent with the ClinVar “Uncertain” classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33441689-C-T	6	3.72e-6	-7.725	In-Between	0.133	Likely Benign	Likely Benign	0.079	Likely Benign										-1.71	Neutral	0.992	Probably Damaging	0.684	Possibly Damaging	2.66	Benign	0.01	Affected	4.32	2	-3	2	3.6	30.03
c.2225G>A	R742Q 2D AIThe SynGAP1 missense variant R742Q is listed in ClinVar (ID 928481.0) with an uncertain significance annotation and is observed in gnomAD (variant ID 6‑33441690‑G‑A). Consensus from multiple in‑silico predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—uniformly classify the change as benign. No tool in the dataset reports a pathogenic prediction. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. A protein‑folding stability analysis via Foldetta is not available for this variant. Overall, the computational evidence strongly favors a benign interpretation, which is consistent with the ClinVar uncertain status rather than contradicting it. The variant is most likely benign, and this assessment does not contradict its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		2	6-33441690-G-A	24	1.49e-5	-4.090	Likely Benign	0.068	Likely Benign	Likely Benign	0.054	Likely Benign										-0.19	Neutral	0.032	Benign	0.007	Benign	2.73	Benign	0.07	Tolerated	4.32	2	1	1	1.0	-28.06
c.2239G>C	V747L 2D AIThe SynGAP1 missense variant V747L (ClinVar ID 1985039.0) is listed as ClinVar status Uncertain and is present in gnomAD (6‑33441704‑G‑C). 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 stability analysis is unavailable. Overall, the majority of computational evidence supports a benign classification, which is consistent with the ClinVar Uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33441704-G-C	2	1.24e-6	-2.790	Likely Benign	0.096	Likely Benign	Likely Benign	0.047	Likely Benign										-0.52	Neutral	0.065	Benign	0.033	Benign	2.67	Benign	0.00	Affected	4.32	2	2	1	-0.4	14.03
c.223G>A	E75K 2D AIThe SynGAP1 missense variant E75K is listed in ClinVar as Benign (ClinVar ID 3360083.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign/Likely benign		2				-4.020	Likely Benign	0.358	Ambiguous	Likely Benign	0.134	Likely Benign										-1.12	Neutral	0.748	Possibly Damaging	0.017	Benign	4.07	Benign	0.00	Affected			0	1	-0.4	-0.94
c.2243T>G	L748R 2D AIThe SynGAP1 missense variant L748R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441708‑T‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Conflicting		2	6-33441708-T-G	3	1.86e-6	-3.331	Likely Benign	0.245	Likely Benign	Likely Benign	0.055	Likely Benign										-0.67	Neutral	0.912	Possibly Damaging	0.448	Possibly Damaging	2.73	Benign	0.02	Affected	4.32	2	-3	-2	-8.3	43.03
c.2245C>T	R749W 2D AIThe SynGAP1 missense variant R749W is listed in ClinVar as benign and is observed in gnomAD (ID 6‑33441710‑C‑T). Prediction tools that classify the variant as benign include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign, and Foldetta stability analysis is unavailable. Overall, the majority of evidence, especially from high‑confidence methods, supports a benign effect. This consensus aligns with the ClinVar designation, so there is no contradiction between the predictions and the reported clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Likely Benign		1	6-33441710-C-T	3	1.86e-6	-7.647	In-Between	0.338	Likely Benign	Likely Benign	0.173	Likely Benign										-2.62	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	2	2	-3	3.6	30.03
c.2246G>A	R749Q 2D AIThe SynGAP1 missense variant R749Q is listed in ClinVar (ID 793884.0) as Benign and is present in gnomAD (6‑33441711‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports 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—including high‑accuracy predictions—supports a benign classification, which is consistent with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Likely Benign		1	6-33441711-G-A	4	2.48e-6	-3.069	Likely Benign	0.212	Likely Benign	Likely Benign	0.152	Likely Benign										-1.00	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.64	Benign	0.03	Affected	4.32	2	1	1	1.0	-28.06
c.2249G>A	G750E 2D AISynGAP1 missense variant G750E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1				-2.618	Likely Benign	0.413	Ambiguous	Likely Benign	0.146	Likely Benign										-2.27	Neutral	1.000	Probably Damaging	0.982	Probably Damaging	2.49	Pathogenic	0.01	Affected	3.99	5	0	-2	-3.1	72.06
c.2255C>T	S752L 2D AIThe SynGAP1 missense variant S752L is listed in ClinVar with an “Uncertain” status (ClinVar ID 2143952.0) and is present in gnomAD (ID 6‑33441720‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		2	6-33441720-C-T	6	3.72e-6	-3.386	Likely Benign	0.182	Likely Benign	Likely Benign	0.195	Likely Benign										-2.09	Neutral	0.993	Probably Damaging	0.641	Possibly Damaging	1.51	Pathogenic	0.01	Affected	3.99	5	-3	-2	4.6	26.08
c.2270G>C	G757A 2D AIThe SynGAP1 missense change G757A is catalogued in ClinVar (ID 3635272.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction algorithms uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool in the dataset predicts pathogenicity. High‑accuracy consensus methods corroborate this view: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect, and AlphaMissense‑Optimized also predicts benign. The Foldetta stability assessment is unavailable for this variant. Taken together, the evidence overwhelmingly supports a benign interpretation, 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		Uncertain		1				-2.626	Likely Benign	0.091	Likely Benign	Likely Benign	0.066	Likely Benign										-0.45	Neutral	0.267	Benign	0.127	Benign	2.73	Benign	0.35	Tolerated			1	0	2.2	14.03
c.2275A>C	M759L 2D AIThe SynGAP1 missense variant M759L is listed in ClinVar with an uncertain significance (ClinVar ID 942432.0) and is present in gnomAD (gnomAD ID 6‑33441740‑A‑C). 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 classifications. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: 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 impact, 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		Uncertain		1	6-33441740-A-C	2	1.24e-6	-2.431	Likely Benign	0.093	Likely Benign	Likely Benign	0.048	Likely Benign										-0.53	Neutral	0.002	Benign	0.005	Benign	2.84	Benign	1.00	Tolerated	3.99	5	4	2	1.9	-18.03
c.2277G>A	M759I 2D AIThe SynGAP1 missense variant M759I is listed in ClinVar (ID 3686687.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441742‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33441742-G-A	1	6.20e-7	-4.058	Likely Benign	0.393	Ambiguous	Likely Benign	0.075	Likely Benign										-0.88	Neutral	0.454	Possibly Damaging	0.192	Benign	2.83	Benign	0.34	Tolerated	3.99	5	1	2	2.6	-18.03
c.227C>G	S76C 2D AIThe SynGAP1 missense variant S76C is listed in ClinVar with an “Uncertain” status (ClinVar ID 1951273.0) and is present in the gnomAD database (gnomAD ID 6‑33425835‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available for this variant. Overall, the majority of computational evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33425835-C-G	2	1.24e-6	-5.408	Likely Benign	0.100	Likely Benign	Likely Benign	0.076	Likely Benign										-1.78	Neutral	0.992	Probably Damaging	0.869	Possibly Damaging	3.71	Benign	0.00	Affected	4.32	1	0	-1	3.3	16.06
c.2282G>A	R761Q 2D AIThe SynGAP1 missense variant R761Q is listed in ClinVar (ID 2882770.0) with an “Uncertain” status and is present in gnomAD (6‑33441747‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33441747-G-A	11	6.81e-6	-4.187	Likely Benign	0.202	Likely Benign	Likely Benign	0.191	Likely Benign										-0.63	Neutral	0.996	Probably Damaging	0.878	Possibly Damaging	2.75	Benign	0.40	Tolerated	3.99	5	1	1	1.0	-28.06
c.2282G>C	R761P 2D AIThe SynGAP1 missense variant R761P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441747‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		3	6-33441747-G-C	1	6.20e-7	-5.091	Likely Benign	0.640	Likely Pathogenic	Likely Benign	0.201	Likely Benign										-1.89	Neutral	0.999	Probably Damaging	0.968	Probably Damaging	2.69	Benign	0.38	Tolerated	3.99	5	0	-2	2.9	-59.07
c.2291A>G	N764S 2D AIThe SynGAP1 missense variant N764S is listed in ClinVar as Benign (ClinVar ID 1948460.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, consistent with the ClinVar classification, and there is no contradiction between the predictions and the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1				-3.149	Likely Benign	0.159	Likely Benign	Likely Benign	0.058	Likely Benign										-0.84	Neutral	0.992	Probably Damaging	0.846	Possibly Damaging	2.65	Benign	0.61	Tolerated	3.64	6	1	1	2.7	-27.03
c.2294G>A	S765N 2D AIThe SynGAP1 missense variant S765N (ClinVar ID 2979632.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PolyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, which is consistent with the ClinVar “Uncertain” classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-5.098	Likely Benign	0.378	Ambiguous	Likely Benign	0.094	Likely Benign										-0.94	Neutral	0.985	Probably Damaging	0.950	Probably Damaging	4.11	Benign	0.06	Tolerated	3.64	6	1	1	-2.7	27.03
c.2299A>G	I767V 2D AIThe SynGAP1 missense variant I767V is listed in ClinVar (ID 1402700.0) with an “Uncertain” clinical significance and is not reported in 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 all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” outcome. No tool predicts pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta stability predictions) has no available result for this variant. Overall, the computational evidence strongly supports a benign effect, 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		Uncertain		1				-2.791	Likely Benign	0.064	Likely Benign	Likely Benign	0.096	Likely Benign										0.10	Neutral	0.072	Benign	0.029	Benign	4.21	Benign	1.00	Tolerated	3.64	6	4	3	-0.3	-14.03
c.2300T>C	I767T 2D AIThe SynGAP1 missense variant I767T is listed in ClinVar (ID 1044161.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, creating a single discordant prediction. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, and AlphaMissense‑Optimized also reports benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-3.749	Likely Benign	0.252	Likely Benign	Likely Benign	0.138	Likely Benign										-0.78	Neutral	0.625	Possibly Damaging	0.249	Benign	4.12	Benign	0.46	Tolerated	3.64	6	0	-1	-5.2	-12.05
c.2302G>A	D768N 2D AIThe SynGAP1 missense variant D768N is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442460‑G‑A). 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 of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus is “Likely Benign,” and Foldetta data are unavailable. Overall, the consensus of available predictions indicates that the variant is most likely benign, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33442460-G-A	2	2.57e-6	-6.892	Likely Benign	0.453	Ambiguous	Likely Benign	0.048	Likely Benign										-0.77	Neutral	0.106	Benign	0.009	Benign	4.07	Benign	0.96	Tolerated	3.64	6	1	2	0.0	-0.98
c.2302G>T	D768Y 2D AIThe SynGAP1 missense variant D768Y is listed in ClinVar with status “Uncertain” (ClinVar ID 1061652.0) and is present in gnomAD (variant ID 6‑33442460‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar designation of uncertainty. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Uncertain		1	6-33442460-G-T			-9.866	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous	0.234	Likely Benign										-2.86	Deleterious	0.989	Probably Damaging	0.806	Possibly Damaging	4.01	Benign	0.07	Tolerated	3.64	6	-4	-3	2.2	48.09
c.2305C>T	L769F 2D AIThe SynGAP1 missense variant L769F is listed in ClinVar (ID 3617309.0) 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) 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—suggest the variant is most likely benign, which is consistent with its ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-5.044	Likely Benign	0.146	Likely Benign	Likely Benign	0.060	Likely Benign										-0.89	Neutral	0.925	Possibly Damaging	0.510	Possibly Damaging	3.94	Benign	0.02	Affected			2	0	-1.0	34.02
c.2324G>A	R775Q 2D AIThe SynGAP1 missense variant R775Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442482‑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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (derived from the same set of high‑confidence predictors) is “Likely Benign.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, 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		Conflicting		3	6-33442482-G-A	11	1.41e-5	-4.476	Likely Benign	0.229	Likely Benign	Likely Benign	0.085	Likely Benign										-0.63	Neutral	0.969	Probably Damaging	0.863	Possibly Damaging	4.17	Benign	0.16	Tolerated	3.64	6	1	1	1.0	-28.06																10.1016/j.ajhg.2020.11.011
c.2324G>C	R775P 2D AIThe SynGAP1 missense variant R775P (ClinVar ID 2959355.0) is classified as Benign in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, consistent with the ClinVar designation, and there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1				-5.072	Likely Benign	0.452	Ambiguous	Likely Benign	0.168	Likely Benign										-0.79	Neutral	0.971	Probably Damaging	0.944	Probably Damaging	4.13	Benign	0.07	Tolerated	3.64	6	-2	0	2.9	-59.07
c.2339C>G	S780C 2D AIThe SynGAP1 missense variant S780C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442891‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a pathogenic outcome; ESM1b is inconclusive and therefore treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are not reported and thus unavailable. Based on the collective predictions, the variant is most likely benign, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		4	6-33442891-C-G	16	9.94e-6	-7.603	In-Between	0.278	Likely Benign	Likely Benign	0.078	Likely Benign										-1.41	Neutral	0.065	Benign	0.043	Benign	2.59	Benign	0.10	Tolerated	3.64	6	-1	0	3.3	16.06
c.233G>T	R78L 2D AIThe SynGAP1 missense variant R78L is listed in ClinVar (ID 3390541.0) 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‑Optimized, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as 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 contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-3.389	Likely Benign	0.635	Likely Pathogenic	Likely Benign	0.062	Likely Benign										-1.59	Neutral	0.385	Benign	0.021	Benign	3.84	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.2343G>A	M781I 2D AIThe SynGAP1 missense variant M781I is listed in ClinVar (ID 2802065.0) as Benign and is not reported in 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: 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, has no available result for this variant. Overall, the predictions strongly support a benign effect, consistent with the ClinVar designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1				-2.484	Likely Benign	0.323	Likely Benign	Likely Benign	0.101	Likely Benign										0.05	Neutral	0.000	Benign	0.001	Benign	2.89	Benign	1.00	Tolerated	3.64	6	1	2	2.6	-18.03
c.2349G>A	M783I 2D AIThe SynGAP1 missense variant M783I is listed in ClinVar as a benign alteration (ClinVar ID 3618151.0) and is present in the gnomAD database (gnomAD ID 6‑33442901‑G‑A). 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). No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a likely benign effect. The Foldetta protein‑folding stability analysis is not available for this variant. Overall, the computational evidence strongly suggests that the variant is most likely benign, in agreement with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1	6-33442901-G-A	6	3.72e-6	-3.560	Likely Benign	0.418	Ambiguous	Likely Benign	0.042	Likely Benign										-0.54	Neutral	0.004	Benign	0.006	Benign	2.87	Benign	0.22	Tolerated	3.64	6	1	2	2.6	-18.03
c.2350G>A	A784T 2D AIThe SynGAP1 missense variant A784T is listed in ClinVar (ID 962668.0) as Benign and is not reported in gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. A Foldetta stability analysis is unavailable, so it does not influence the overall interpretation. Based on the unanimous benign predictions and the ClinVar designation, the variant is most likely benign, with no contradiction to the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1				-3.579	Likely Benign	0.089	Likely Benign	Likely Benign	0.046	Likely Benign										1.23	Neutral	0.001	Benign	0.006	Benign	2.92	Benign	1.00	Tolerated	3.64	6	1	0	-2.5	30.03
c.2353C>T	R785C 2D AIThe SynGAP1 R785C missense variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442905‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points toward a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	Uncertain		1	6-33442905-C-T	29	1.80e-5	-5.887	Likely Benign	0.662	Likely Pathogenic	Likely Benign	0.126	Likely Benign										-5.06	Deleterious	0.144	Benign	0.046	Benign	2.22	Pathogenic	0.00	Affected	3.64	6	-4	-3	7.0	-53.05
c.2354G>A	R785H 2D AIThe SynGAP1 R785H missense variant (ClinVar ID 2321588.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (ID 6‑33442906‑G‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, does not provide a result for this variant. Overall, the majority of computational predictions (five pathogenic versus three benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current predictions, 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.		SH3-binding motif	Uncertain		2	6-33442906-G-A	4	2.50e-6	-4.782	Likely Benign	0.388	Ambiguous	Likely Benign	0.129	Likely Benign										-2.61	Deleterious	0.999	Probably Damaging	0.947	Probably Damaging	2.25	Pathogenic	0.01	Affected	3.64	6	2	0	1.3	-19.05
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	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	-1	0.9	3.99
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	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	-1	1	0.8	-10.04
c.2362T>A	S788T 2D AIThe SynGAP1 missense variant S788T is listed in ClinVar with an uncertain significance (ClinVar ID 392728.0) and is present in the gnomAD database (gnomAD ID 6‑33442914‑T‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score, which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. Tools that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (majority vote) also favors a benign interpretation. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	Uncertain		2	6-33442914-T-A	4	2.49e-6	-4.288	Likely Benign	0.288	Likely Benign	Likely Benign	0.092	Likely Benign										-2.25	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	1.55	Pathogenic	0.02	Affected	3.64	6	1	1	0.1	14.03
c.2369C>A	T790N 2D AIThe SynGAP1 missense variant T790N is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33442921‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable, and Foldetta results are not reported. Overall, the majority of conventional tools (5 pathogenic vs. 4 benign) lean toward a pathogenic interpretation, while the single high‑accuracy tool suggests benign. The variant’s ClinVar status remains uncertain, so there is no contradiction with the current clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Conflicting		3	6-33442921-C-A	69	4.28e-5	-5.243	Likely Benign	0.276	Likely Benign	Likely Benign	0.103	Likely Benign										-2.54	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.27	Pathogenic	0.02	Affected	3.64	6	0	0	-2.8	13.00
c.2369C>G	T790S 2D AIThe SynGAP1 missense variant T790S is listed in ClinVar (ID 1020340.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM 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	SH3-binding motif	Uncertain		1				-3.914	Likely Benign	0.123	Likely Benign	Likely Benign	0.134	Likely Benign										-1.83	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.39	Pathogenic	0.33	Tolerated	3.64	6	1	1	-0.1	-14.03
c.2381C>T	P794L 2D AIThe SynGAP1 missense variant P794L is listed in ClinVar as Benign (ClinVar ID 859213.0) and is present in the gnomAD database (gnomAD ID 6‑33442933‑C‑T). 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 is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the consensus of available predictions indicates that P794L is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	Benign/Likely benign		2	6-33442933-C-T	73	4.52e-5	-3.808	Likely Benign	0.079	Likely Benign	Likely Benign	0.075	Likely Benign										-0.80	Neutral	0.761	Possibly Damaging	0.321	Benign	4.24	Benign	0.03	Affected	4.07	3	-3	-3	5.4	16.04
c.2393C>T	P798L 2D AIThe SynGAP1 missense variant P798L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442945‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; a Foldetta stability prediction is not available. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	Uncertain		2	6-33442945-C-T	6	3.72e-6	-5.640	Likely Benign	0.074	Likely Benign	Likely Benign	0.042	Likely Benign										-0.86	Neutral	0.981	Probably Damaging	0.631	Possibly Damaging	4.21	Benign	0.00	Affected	4.32	1	-3	-3	5.4	16.04
c.2401G>A	G801S 2D AIThe SynGAP1 missense variant G801S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in‑silico predictors classify the change as benign: SGM‑Consensus (Likely 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 benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the evidence strongly supports 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	SH3-binding motif	Uncertain		1				-3.665	Likely Benign	0.087	Likely Benign	Likely Benign	0.039	Likely Benign										-0.41	Neutral	0.009	Benign	0.019	Benign	2.76	Benign	0.48	Tolerated	4.32	2	0	1	-0.4	30.03
c.2405G>A	G802D 2D AIThe SynGAP1 missense variant G802D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (6‑33442957‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the change as benign. No tool predicts a pathogenic outcome. The high‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	Uncertain		1	6-33442957-G-A	1	6.20e-7	-5.083	Likely Benign	0.476	Ambiguous	Likely Benign	0.153	Likely Benign										-0.38	Neutral	0.126	Benign	0.138	Benign	2.72	Benign	0.09	Tolerated	3.77	5	1	-1	-3.1	58.04
c.2408A>G	K803R 2D AIThe SynGAP1 missense variant K803R is listed in ClinVar (ID 834618.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—SIFT and FATHMM—predict pathogenicity. 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. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	Uncertain		1				-2.281	Likely Benign	0.097	Likely Benign	Likely Benign	0.018	Likely Benign										-1.52	Neutral	0.103	Benign	0.038	Benign	2.38	Pathogenic	0.00	Affected	3.77	5	3	2	-0.6	28.01
c.2414T>C	L805P 2D AIThe SynGAP1 missense variant L805P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a pathogenic outcome from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and no Foldetta data are available. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Uncertain		1				-4.661	Likely Benign	0.444	Ambiguous	Likely Benign	0.272	Likely Benign										-3.40	Deleterious	0.975	Probably Damaging	0.767	Possibly Damaging	2.36	Pathogenic	0.00	Affected	3.77	5	-3	-3	-5.4	-16.04
c.2420A>G	Y807C 2D AIThe SynGAP1 missense variant Y807C is listed in ClinVar with an “Uncertain” status (ClinVar ID 2119812.0) and is present in gnomAD (ID 6‑33442972‑A‑G). Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic interpretation, whereas AlphaMissense‑Optimized alone suggests benign. The variant is most likely pathogenic based on the collective evidence, and this conclusion is not contradicted by the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Uncertain		1	6-33442972-A-G	1	6.20e-7	-7.228	In-Between	0.204	Likely Benign	Likely Benign	0.243	Likely Benign										-3.89	Deleterious	0.997	Probably Damaging	0.934	Probably Damaging	2.42	Pathogenic	0.01	Affected	3.77	5	0	-2	3.8	-60.04
c.2420A>T	Y807F 2D AIThe SynGAP1 missense variant Y807F is listed in ClinVar (ID 1491782.0) with an “Uncertain” status and is not reported in 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 all return benign scores, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No tool in the set predicts pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the four high‑accuracy predictors) is benign. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available result for this variant. Overall, the computational evidence strongly supports 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	Uncertain		1				-3.667	Likely Benign	0.073	Likely Benign	Likely Benign	0.057	Likely Benign										0.14	Neutral	0.012	Benign	0.022	Benign	2.92	Benign	0.98	Tolerated	3.77	5	7	3	4.1	-16.00
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	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	1	-1	0.8	-10.04
c.2435C>A	P812H 2D AIThe SynGAP1 missense variant P812H is listed in ClinVar with an uncertain significance and is present in the gnomAD database (ID 6‑33442987‑C‑A). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic outcome; ESM1b remains uncertain. High‑accuracy methods give a benign result from AlphaMissense‑Optimized, a pathogenic consensus from the SGM approach (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta data are unavailable. Overall, the balance of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Uncertain		2	6-33442987-C-A	3	1.86e-6	-7.470	In-Between	0.698	Likely Pathogenic	Likely Benign	0.272	Likely Benign										-2.81	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.00	Affected	4.32	4	0	-2	-1.6	40.02
c.2443C>A	R815S 2D AISynGAP1 R815S is listed in ClinVar as Benign (ID 3645150.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus as Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of predictions lean toward pathogenicity, whereas the consensus and high‑accuracy tools suggest benignity. Thus, the variant is most likely pathogenic based on the prevailing predictions, contradicting its ClinVar benign designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Benign		1				-7.324	In-Between	0.950	Likely Pathogenic	Ambiguous	0.138	Likely Benign										-1.86	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.02	Affected			0	-1	3.7	-69.11
c.2443C>G	R815G 2D AISynGAP1 missense variant R815G is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on benign effect include REVEL and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Uncertain calls are made by ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Uncertain		1				-7.983	In-Between	0.854	Likely Pathogenic	Ambiguous	0.146	Likely Benign										-3.22	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.02	Affected	4.32	4	-3	-2	4.1	-99.14
c.2443C>T	R815C 2D AIThe SynGAP1 missense variant R815C is listed in ClinVar (ID 660618.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442995‑C‑T). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is “Uncertain.” The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	Uncertain		1	6-33442995-C-T	5	3.10e-6	-9.373	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous	0.174	Likely Benign										-3.89	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	4	-4	-3	7.0	-53.05
c.2444G>A	R815H 2D AIThe SynGAP1 missense variant R815H (ClinVar ID 833773.0) is classified as benign in ClinVar and is present in gnomAD (6‑33442996‑G‑A). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar) and SIFT. Two tools report uncertainty: ESM1b and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the balance of evidence favors a benign effect, consistent with the ClinVar annotation and with no conflict regarding its status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	Likely Benign		2	6-33442996-G-A	24	1.49e-5	-7.474	In-Between	0.553	Ambiguous	Likely Benign	0.157	Likely Benign										-1.81	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.02	Affected	4.32	4	2	0	1.3	-19.05																10.1016/j.ajhg.2020.11.011
c.2444G>T	R815L 2D AISynGAP1 missense variant R815L is listed in ClinVar (ID 2505666.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools indicates a pathogenic effect, which contrasts with the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	Uncertain		1				-8.546	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.175	Likely Benign										-3.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.03	Affected	4.32	4	-2	-3	8.3	-43.03
c.2458T>A	Y820N 2D AIThe SynGAP1 Y820N variant is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default all predict a pathogenic outcome. AlphaMissense‑Optimized returns an “Uncertain” result. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are evenly split between benign and pathogenic, with no high‑confidence pathogenic or benign signal. Thus, the variant is most likely of uncertain significance, which is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1				-9.032	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.143	Likely Benign										-1.53	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.74	Benign	0.20	Tolerated			-2	-2	-2.2	-49.07
c.2459A>G	Y820C 2D AIThe SynGAP1 missense variant Y820C 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, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence—including the SGM‑Consensus—suggests the variant is most likely pathogenic, a conclusion that does not contradict the current ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Uncertain		1				-8.797	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	0.113	Likely Benign										-3.16	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.68	Benign	0.06	Tolerated	3.77	5	0	-2	3.8	-60.04
c.2474C>T	S825L 2D AIThe SynGAP1 missense variant S825L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443026‑C‑T). 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, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Uncertain		1	6-33443026-C-T	1	6.20e-7	-4.987	Likely Benign	0.910	Likely Pathogenic	Ambiguous	0.249	Likely Benign										-4.30	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.94	Pathogenic	0.01	Affected	3.77	5	-2	-3	4.6	26.08
c.2485G>A	E829K 2D AIThe SynGAP1 missense variant E829K is listed in ClinVar as Pathogenic (ClinVar ID 1721258.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only REVEL predicts a benign outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E829K is most likely pathogenic, and this conclusion aligns with the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Pathogenic		1				-7.527	In-Between	0.807	Likely Pathogenic	Ambiguous	0.194	Likely Benign										-2.65	Deleterious	0.994	Probably Damaging	0.900	Possibly Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0	1	-0.4	-0.94
c.2493G>C	E831D 2D AIThe SynGAP1 missense variant E831D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443045‑G‑C). All available in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely‑pathogenic outcome. Grouping by agreement, the benign‑predicting tools comprise the entire set, while no pathogenic predictions are present. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign classification. Foldetta results are unavailable. Overall, the computational evidence strongly supports 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		Uncertain		1	6-33443045-G-C	1	6.19e-7	-3.055	Likely Benign	0.063	Likely Benign	Likely Benign	0.073	Likely Benign										1.23	Neutral	0.002	Benign	0.002	Benign	2.64	Benign	0.77	Tolerated	3.77	5	3	2	0.0	-14.03
c.249A>T	R83S 2D AISynGAP1 R83S is listed in ClinVar (ID 537001.0) with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign; Foldetta results are unavailable. Overall, the predictions are split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools are discordant. Thus, the variant is most likely pathogenic based on the predominance of pathogenic predictions, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-2.550	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic	0.094	Likely Benign										-1.87	Neutral	0.909	Possibly Damaging	0.587	Possibly Damaging	3.19	Benign	0.00	Affected	4.32	1	0	-1	3.7	-69.11
c.2502G>C	M834I 2D AIThe SynGAP1 missense variant M834I is listed in ClinVar (ID 3007819.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT classifies the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the collective predictions indicate that M834I is most likely benign, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-3.377	Likely Benign	0.291	Likely Benign	Likely Benign	0.055	Likely Benign										-1.21	Neutral	0.026	Benign	0.009	Benign	2.56	Benign	0.00	Affected	4.32	4	1	2	2.6	-18.03
c.2503C>A	L835M 2D AIThe SynGAP1 missense variant L835M is listed in ClinVar (ID 2731331.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus also indicating a likely benign outcome, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence—including the high‑accuracy tools—supports a benign classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1				-4.153	Likely Benign	0.121	Likely Benign	Likely Benign	0.068	Likely Benign										-0.45	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.67	Benign	0.12	Tolerated	3.77	5	2	4	-1.9	18.03
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		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	1	0	0.4	-30.03
c.250C>G	R84G 2D AIThe SynGAP1 missense variant R84G is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the majority of available predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar status of “Uncertain.” Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1				-6.627	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic	0.139	Likely Benign										-2.64	Deleterious	0.962	Probably Damaging	0.726	Possibly Damaging	3.68	Benign	0.00	Affected	4.32	1	-3	-2	4.1	-99.14
c.2514C>A	N838K 2D AIThe SynGAP1 missense variant N838K is listed in ClinVar with an “Uncertain” status (ClinVar ID 1377909.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence leans toward a pathogenic interpretation, 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		Uncertain		2				-8.470	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	0.097	Likely Benign										-2.78	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.69	Benign	0.16	Tolerated	3.77	5	1	0	-0.4	14.07
c.2518A>T	S840C 2D AIThe SynGAP1 missense variant S840C is listed in ClinVar (ID 2089808.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta results are unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for S840C. This conclusion aligns with the ClinVar designation of uncertainty rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Uncertain		1				-8.799	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.376	Likely Benign										-3.96	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	1.50	Pathogenic	0.00	Affected	3.77	5	0	-1	3.3	16.06
c.2521G>A	V841M 2D AISynGAP1 variant V841M is listed in ClinVar with an uncertain significance and is present in gnomAD (6-33443073-G-A). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The ESM1b score is inconclusive. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta stability analysis is unavailable. Taken together, the majority of evidence, including the high‑accuracy tools, points to a benign effect for V841M. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1	6-33443073-G-A	3	1.86e-6	-7.000	In-Between	0.651	Likely Pathogenic	Likely Benign	0.119	Likely Benign										-0.74	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.54	Benign	0.02	Affected	3.77	5	1	2	-2.3	32.06
c.2522T>C	V841A 2D AIThe SynGAP1 missense variant V841A (ClinVar ID 1395978.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443074‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool reports an uncertain outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (two pathogenic, two benign) and is therefore inconclusive. No Foldetta stability assessment is available for this variant. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1	6-33443074-T-C	3	1.86e-6	-8.152	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous	0.183	Likely Benign										-2.13	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.57	Benign	0.02	Affected	3.77	5	0	0	-2.4	-28.05
c.2525C>A	S842Y 2D AIThe SynGAP1 missense variant S842Y is listed in ClinVar as Pathogenic (ClinVar ID 624244.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, in agreement with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		Likely Pathogenic		1				-16.124	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.191	Likely Benign										-4.28	Deleterious	0.944	Possibly Damaging	0.676	Possibly Damaging	1.97	Pathogenic	0.00	Affected	3.77	5	-3	-2	-0.5	76.10
c.2548G>A	G850R 2D AIThe SynGAP1 missense variant G850R is listed in ClinVar with an uncertain significance (ClinVar ID 2042462.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only SIFT predicts a pathogenic effect, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign and the SGM‑Consensus indicating a likely benign outcome; Foldetta, a protein‑folding stability method, did not provide a result for this substitution. Overall, the preponderance of evidence points to a benign impact, which aligns with the ClinVar designation of uncertain significance rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-5.082	Likely Benign	0.398	Ambiguous	Likely Benign	0.194	Likely Benign										-0.07	Neutral	0.010	Benign	0.010	Benign	4.30	Benign	0.01	Affected	3.77	5	-3	-2	-4.1	99.14
c.2557G>C	G853R 2D AIThe SynGAP1 missense variant G853R 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‑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 (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy predictions therefore point to a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and no Foldetta data is available. Overall, the majority of evidence supports a benign classification, which does not contradict the current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-4.749	Likely Benign	0.366	Ambiguous	Likely Benign	0.091	Likely Benign										-1.27	Neutral	0.846	Possibly Damaging	0.624	Possibly Damaging	4.18	Benign	0.00	Affected			-3	-2	-4.1	99.14
c.2560C>T	R854C 2D AIThe SynGAP1 missense variant R854C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33443112‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available. Overall, the majority of computational evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33443112-C-T	3	1.86e-6	-5.082	Likely Benign	0.170	Likely Benign	Likely Benign	0.174	Likely Benign										-2.48	Neutral	1.000	Probably Damaging	0.947	Probably Damaging	4.05	Benign	0.01	Affected	3.88	3	-3	-4	7.0	-53.05
c.2561G>A	R854H 2D AIThe SynGAP1 missense variant R854H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443113‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33443113-G-A	4	2.48e-6	-3.686	Likely Benign	0.094	Likely Benign	Likely Benign	0.183	Likely Benign										-1.38	Neutral	0.997	Probably Damaging	0.899	Possibly Damaging	4.07	Benign	0.04	Affected	3.88	3	2	0	1.3	-19.05
c.2567A>G	N856S 2D AIThe SynGAP1 missense variant N856S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443119‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also benign; Foldetta results are unavailable. 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		Uncertain		1	6-33443119-A-G	2	1.24e-6	-2.104	Likely Benign	0.064	Likely Benign	Likely Benign	0.040	Likely Benign										-1.54	Neutral	0.901	Possibly Damaging	0.535	Possibly Damaging	4.16	Benign	0.30	Tolerated	3.88	3	1	1	2.7	-27.03
c.256G>A	V86I 2D AIThe SynGAP1 missense variant V86I is listed in ClinVar (ID 588267.0) with an “Uncertain” status and is not reported in gnomAD. 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 variant as benign or likely benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the majority of predictions indicate that V86I is most likely benign, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1				-4.726	Likely Benign	0.338	Likely Benign	Likely Benign	0.076	Likely Benign										-0.31	Neutral	0.267	Benign	0.097	Benign	3.94	Benign	0.00	Affected	4.32	1	4	3	0.3	14.03
c.2573G>A	S858N 2D AIThe SynGAP1 missense variant S858N is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443125‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 HumVar and SIFT predict pathogenicity, but these two tools are in the minority. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, 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		Uncertain		1	6-33443125-G-A	2	1.24e-6	-4.311	Likely Benign	0.121	Likely Benign	Likely Benign	0.107	Likely Benign										-0.67	Neutral	0.448	Benign	0.846	Possibly Damaging	4.13	Benign	0.02	Affected	3.77	5	1	1	-2.7	27.03
c.2578G>A	V860I 2D AIThe SynGAP1 missense variant V860I is catalogued in ClinVar as a benign alteration (ClinVar ID 411591.0) and is present in the gnomAD database (gnomAD ID 6‑33443130‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized returns 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 consensus of computational evidence strongly favors a benign impact, aligning with the ClinVar designation and showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Benign		1	6-33443130-G-A	21	1.30e-5	-4.516	Likely Benign	0.095	Likely Benign	Likely Benign	0.039	Likely Benign										-0.42	Neutral	0.009	Benign	0.006	Benign	4.24	Benign	0.00	Affected	3.77	5	4	3	0.3	14.03
c.2582C>T	S861L 2D AIThe SynGAP1 missense variant S861L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443134‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. No Foldetta stability prediction is available for this variant. Overall, the computational evidence overwhelmingly 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		Uncertain		1	6-33443134-C-T	2	1.24e-6	-4.966	Likely Benign	0.219	Likely Benign	Likely Benign	0.144	Likely Benign										-2.10	Neutral	0.904	Possibly Damaging	0.355	Benign	3.93	Benign	0.07	Tolerated	4.32	3	-3	-2	4.6	26.08
c.2591C>T	A864V 2D AIThe SynGAP1 missense variant A864V is listed in ClinVar with an uncertain significance (ClinVar ID 655662.0) and is observed in gnomAD (ID 6‑33443143‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, which does not contradict its current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		2	6-33443143-C-T	6	3.72e-6	-4.749	Likely Benign	0.126	Likely Benign	Likely Benign	0.038	Likely Benign										-1.35	Neutral	0.767	Possibly Damaging	0.119	Benign	2.45	Pathogenic	0.30	Tolerated	3.82	4	0	0	2.4	28.05
c.2596G>A	V866I 2D AIThe SynGAP1 missense variant V866I is listed in ClinVar with an “Uncertain” status (ClinVar ID 536995.0) and is present in gnomAD (6‑33443148‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus 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		Conflicting		3	6-33443148-G-A	5	3.10e-6	-4.652	Likely Benign	0.118	Likely Benign	Likely Benign	0.059	Likely Benign										-0.39	Neutral	0.957	Probably Damaging	0.541	Possibly Damaging	2.69	Benign	0.27	Tolerated	3.82	4	4	3	0.3	14.03
c.2596G>T	V866L 2D AIThe SynGAP1 missense variant V866L is listed in ClinVar (ID 469150.0) with an “Uncertain” clinical significance and is present in gnomAD (6‑33443148‑G‑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 outcome. 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, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign effect, 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		Uncertain		1	6-33443148-G-T	1	6.20e-7	-3.352	Likely Benign	0.148	Likely Benign	Likely Benign	0.046	Likely Benign										-0.97	Neutral	0.217	Benign	0.229	Benign	2.71	Benign	0.21	Tolerated	3.82	4	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		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	2	1	0.4	-14.03
c.2619C>G	S873R 2D AIThe SynGAP1 missense variant S873R is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33443171‑C‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a pathogenic effect, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		1	6-33443171-C-G	1	6.20e-7	-5.856	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic	0.192	Likely Benign										-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.06	Tolerated	3.77	5	0	-1	-3.7	69.11
c.2623G>A	A875T 2D AIThe SynGAP1 missense variant A875T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443175‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” 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 preponderance of evidence points to a benign impact, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		Uncertain		1	6-33443175-G-A	1	6.20e-7	-3.793	Likely Benign	0.179	Likely Benign	Likely Benign	0.110	Likely Benign										-1.56	Neutral	0.972	Probably Damaging	0.864	Possibly Damaging	2.72	Benign	0.26	Tolerated	3.77	5	0	1	-2.5	30.03
c.2627C>T	S876L 2D AISynGAP1 variant S876L is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect; the SGM Consensus, derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive and therefore unavailable; Foldetta stability analysis is also unavailable. Overall, the majority of available predictions favor a benign impact, suggesting the variant is most likely benign. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			Uncertain		2				-5.856	Likely Benign	0.489	Ambiguous	Likely Benign	0.249	Likely Benign										-3.56	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.57	Benign	0.05	Affected	3.77	5	-2	-3	4.6	26.08
c.2632A>G	T878A 2D AIThe SynGAP1 missense variant T878A is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available 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 likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is 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		Uncertain		1				-2.154	Likely Benign	0.081	Likely Benign	Likely Benign	0.088	Likely Benign										-0.67	Neutral	0.003	Benign	0.006	Benign	2.73	Benign	0.18	Tolerated	3.77	5	1	0	2.5	-30.03