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

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.1558T>G	S520A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S520A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized, whereas a larger group—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. The premPS score is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy consensus is split, but the pathogenic predictions dominate. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000											-8.417	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.2	0.19	Likely Benign	0.11	Likely Benign	0.56	Ambiguous	0.523	Likely Pathogenic	-2.55	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.4887	0.3636		1	1	2.6	-16.00
c.1559C>A	S520Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of algorithms predict pathogenicity: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give inconclusive results: FoldX (Uncertain) and premPS (Uncertain). High‑accuracy assessments further support a mixed signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000											-13.124	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.93	Ambiguous	0.4	0.16	Likely Benign	-0.39	Likely Benign	0.59	Ambiguous	0.814	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.36	Pathogenic	0.00	Affected			0.0743	0.4563		-3	-2	-0.5	76.10
c.1304T>G	L435W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L435W is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM. The majority of other in silico predictors (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the change as pathogenic, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. Overall, the computational evidence strongly favors 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	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000					Uncertain		1				-14.889	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.11	Destabilizing	0.1	0.69	Ambiguous	1.40	Ambiguous	1.66	Destabilizing	0.572	Likely Pathogenic	-5.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.15	Benign	0.00	Affected	3.37	29	0.0536	0.2496		-2	-2	-4.7	73.05	242.2	-25.2	0.0	0.0	0.3	0.1							X	Potentially Pathogenic	The iso-butyl side chain of Leu435, located in an α helix (res. Met414-Glu436), packs against other hydrophobic residues in an interhelix space (e.g., Val699, Val447, Leu489, Leu439) in the WT simulations. In the variant simulations, the indole ring of Trp435 fits into the same niche despite its considerably bulkier size. Additionally, the side chain forms an H-bond with the backbone carbonyl of Leu696 in an α helix (res. Asp684-Gln702). Although no apparent negative changes are observed during the variant simulation, the size difference between the swapped residues could affect the protein folding process.
c.1559C>G	S520C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520C is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Foldetta, and ESM1b, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default; Rosetta, premPS, and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000											-6.947	Likely Benign	0.917	Likely Pathogenic	Ambiguous	0.05	Likely Benign	0.2	0.76	Ambiguous	0.41	Likely Benign	0.53	Ambiguous	0.720	Likely Pathogenic	-4.57	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.36	Pathogenic	0.03	Affected			0.1029	0.4948		0	-1	3.3	16.06
c.1555G>C	E519Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.693	Likely Pathogenic	0.792	Likely Pathogenic	Ambiguous	-0.35	Likely Benign	0.1	-0.14	Likely Benign	-0.25	Likely Benign	-0.21	Likely Benign	0.195	Likely Benign	-2.48	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	3.28	Benign	0.14	Tolerated			0.1394	0.3418		2	2	0.0	-0.98
c.1553A>T	Y518F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools are uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors (seven benign vs. four pathogenic) support a benign classification, and this does not contradict the ClinVar status, which has no entry for this variant. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-10.617	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.34	Likely Benign	0.1	-0.61	Ambiguous	-0.14	Likely Benign	0.41	Likely Benign	0.318	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.22	Tolerated			0.2107	0.2230		7	3	4.1	-16.00
c.1550T>C	L517P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517P is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-15.546	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.88	Destabilizing	0.8	7.96	Destabilizing	6.92	Destabilizing	1.92	Destabilizing	0.937	Likely Pathogenic	-6.70	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.3570	0.1963		-3	-3	-5.4	-16.04
c.1550T>G	L517R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain outcome is FoldX. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta predicts Pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-14.761	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.75	Ambiguous	0.2	4.33	Destabilizing	3.04	Destabilizing	1.83	Destabilizing	0.936	Likely Pathogenic	-5.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.1202	0.0688		-3	-2	-8.3	43.03
c.1307A>G	E436G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the majority of algorithms (SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, premPS, and Foldetta are inconclusive. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta’s stability prediction is uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.355	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.02	Destabilizing	1.76	Ambiguous	0.58	Ambiguous	0.802	Likely Pathogenic	-6.63	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	4.61	Benign	0.03	Affected			0.2910	0.4841		0	-2	3.1	-72.06
c.1552T>A	Y518N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Foldetta) uniformly predict a pathogenic impact. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta also predicts pathogenicity. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.036	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	2.99	Destabilizing	0.8	1.50	Ambiguous	2.25	Destabilizing	1.29	Destabilizing	0.506	Likely Pathogenic	-8.45	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.04	Affected			0.1791	0.0212		-2	-2	-2.2	-49.07
c.1552T>C	Y518H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y518H, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000					Uncertain		1				-9.797	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.39	Destabilizing	0.4	0.82	Ambiguous	1.61	Ambiguous	1.31	Destabilizing	0.496	Likely Benign	-4.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.08	Tolerated			0.1927	0.0212		0	2	-1.9	-26.03
c.1307A>C	E436A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436A is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include Foldetta, premPS, and FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. Two high‑accuracy predictors give concordant results: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. No prediction is missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for E436A, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.678	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.03	Ambiguous	0.0	-0.88	Ambiguous	0.08	Likely Benign	0.23	Likely Benign	0.825	Likely Pathogenic	-5.68	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	4.65	Benign	0.05	Affected			0.3901	0.5116		0	-1	5.3	-58.04
c.1306G>C	E436Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436Q is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the consensus of pathogenic predictions outweighs benign ones, and the high‑accuracy tools reinforce a pathogenic classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.413	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	1.58	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	0.607	Likely Pathogenic	-2.76	Deleterious	0.992	Probably Damaging	0.946	Probably Damaging	4.64	Benign	0.01	Affected			0.1237	0.5809		2	2	0.0	-0.98
c.1552T>G	Y518D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.247	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.9	2.68	Destabilizing	3.30	Destabilizing	1.36	Destabilizing	0.619	Likely Pathogenic	-9.41	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.03	Affected			0.3682	0.0212		-4	-3	-2.2	-48.09
c.1306G>A	E436K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining evaluated algorithms (REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic impact; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E436K, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000					Uncertain		1				-13.869	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.56	Ambiguous	0.1	2.86	Destabilizing	1.71	Ambiguous	0.82	Ambiguous	0.829	Likely Pathogenic	-3.77	Deleterious	0.994	Probably Damaging	0.951	Probably Damaging	4.71	Benign	0.02	Affected	3.37	29	0.2332	0.5995		0	1	-0.4	-0.94	186.8	39.8	0.0	0.0	-0.2	0.0	X	X		X				Potentially Pathogenic	The carboxylate group of Glu436, located on the α helix (res. Met414-Glu436), forms a salt bridge with the amino group of the Lys444 side chain on an opposing α helix (res. Val441-Ser457). The backbone carbonyl of Glu436 also H-bonds with the Lys444 side chain, which helps keep the ends of the two α helices tightly connected. In contrast, in the variant simulations, the salt bridge formation with Lys444 is not possible. Instead, the repelled Lys436 side chain rotates outward, causing a change in the α helix backbone H-bonding: the amide group of Lys444 H-bonds with the carbonyl of Ala433 instead of the carbonyl of Cys432.
c.1553A>C	Y518S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized is uncertain; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for Y518S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.453	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous	2.76	Destabilizing	0.8	2.45	Destabilizing	2.61	Destabilizing	1.61	Destabilizing	0.551	Likely Pathogenic	-8.38	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.06	Tolerated			0.3948	0.1059		-3	-2	0.5	-76.10
c.1305G>T	L435F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (Likely Pathogenic). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, providing no definitive evidence for either outcome. Given the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-11.871	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	0.95	Ambiguous	0.73	Ambiguous	0.69	Ambiguous	0.222	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.26	Benign	0.01	Affected			0.0587	0.2723		2	0	-1.0	34.02
c.1553A>G	Y518C 2D AIThe SynGAP1 missense variant Y518C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; and uncertain results from Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta predicts pathogenic folding instability. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-9.813	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	2.99	Destabilizing	0.9	1.70	Ambiguous	2.35	Destabilizing	0.69	Ambiguous	0.415	Likely Benign	-8.35	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.16	Tolerated			0.2905	0.1128		0	-2	3.8	-60.04
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	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000					Uncertain		1				-12.541	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	-1.20	Ambiguous	0.4	0.39	Likely Benign	-0.41	Likely Benign	0.25	Likely Benign	0.833	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.36	Pathogenic	0.00	Affected	3.37	35	0.0668	0.4779		-2	-3	3.6	60.10
c.151A>G	I51V 2D AIThe SynGAP1 missense variant I51V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-3.397	Likely Benign	0.195	Likely Benign	Likely Benign										0.065	Likely Benign	-0.24	Neutral	0.004	Benign	0.007	Benign	4.26	Benign	0.00	Affected			0.1330	0.3602		4	3	-0.3	-14.03
c.1525G>T	A509S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumDiv, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Four tools give uncertain or inconclusive results (FoldX, Rosetta, Foldetta, premPS). High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus inconclusive, and Foldetta is also inconclusive. Overall, the majority of standard predictors lean toward pathogenicity, while the most reliable single‑tool prediction (AlphaMissense‑Optimized) suggests benign. Given the balance of evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-9.997	Likely Pathogenic	0.171	Likely Benign	Likely Benign	0.83	Ambiguous	0.1	1.63	Ambiguous	1.23	Ambiguous	0.59	Ambiguous	0.621	Likely Pathogenic	-2.18	Neutral	0.119	Benign	0.468	Possibly Damaging	-1.35	Pathogenic	0.01	Affected			0.2410	0.4384		1	1	-2.6	16.00
c.1526C>A	A509D 2D AIThe SynGAP1 missense variant A509D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Pathogenic” verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-17.026	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	4.02	Destabilizing	1.6	3.09	Destabilizing	3.56	Destabilizing	1.36	Destabilizing	0.915	Likely Pathogenic	-4.94	Deleterious	0.963	Probably Damaging	0.844	Possibly Damaging	-1.40	Pathogenic	0.00	Affected			0.1610	0.1360		0	-2	-5.3	44.01
c.1526C>G	A509G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that clearly indicate benign effect include only AlphaMissense‑Optimized. All other evaluated tools that provide a definitive call predict pathogenicity: SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Tools with inconclusive results (AlphaMissense‑Default, FoldX, and Foldetta) are treated as unavailable and do not influence the overall assessment. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, combining FoldX‑MD (uncertain) and Rosetta (pathogenic), is uncertain. Overall, the majority of definitive predictions support a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-11.873	Likely Pathogenic	0.541	Ambiguous	Likely Benign	1.36	Ambiguous	0.2	2.33	Destabilizing	1.85	Ambiguous	1.14	Destabilizing	0.804	Likely Pathogenic	-3.57	Deleterious	0.911	Possibly Damaging	0.706	Possibly Damaging	-1.39	Pathogenic	0.00	Affected			0.2193	0.4213		1	0	-2.2	-14.03
c.1526C>T	A509V 2D 3DClick to see structure in 3D Viewer AISynGAP1 A509V is not reported in ClinVar and is absent from gnomAD. High‑accuracy predictors give mixed results: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive because FoldX is uncertain and Rosetta is benign. Among the remaining tools, benign predictions come from REVEL, Rosetta, premPS, polyPhen2_HumDiv, polyPhen2_HumVar, and SIFT, whereas pathogenic predictions come from SGM‑Consensus, PROVEAN, ESM1b, and FATHMM. AlphaMissense‑Default and FoldX remain uncertain. Overall, the majority of evidence points toward a benign effect, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-11.987	Likely Pathogenic	0.382	Ambiguous	Likely Benign	0.52	Ambiguous	0.5	0.35	Likely Benign	0.44	Likely Benign	-0.25	Likely Benign	0.474	Likely Benign	-3.11	Deleterious	0.064	Benign	0.048	Benign	-1.15	Pathogenic	0.18	Tolerated			0.1333	0.5706		0	0	2.4	28.05
c.1528A>C	I510L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta)—all indicate a benign effect. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-2.362	Likely Benign	0.116	Likely Benign	Likely Benign	0.31	Likely Benign	0.2	-0.05	Likely Benign	0.13	Likely Benign	-1.01	Stabilizing	0.338	Likely Benign	0.69	Neutral	0.016	Benign	0.130	Benign	-0.74	Pathogenic	1.00	Tolerated			0.0819	0.2461		2	2	-0.7	0.00
c.1528A>G	I510V 2D 3DClick to see structure in 3D Viewer AISynGAP1 I510V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, FATHMM, and premPS. FoldX and Rosetta analyses are inconclusive, and Foldetta stability assessment is unavailable. High‑accuracy methods reinforce the benign trend: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta provides no definitive result. Overall, the majority of evidence points to a benign effect for I510V, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-6.072	Likely Benign	0.136	Likely Benign	Likely Benign	1.45	Ambiguous	0.2	0.50	Ambiguous	0.98	Ambiguous	1.13	Destabilizing	0.461	Likely Benign	-1.00	Neutral	0.792	Possibly Damaging	0.332	Benign	-1.36	Pathogenic	0.02	Affected			0.0999	0.2291		4	3	-0.3	-14.03
c.1528A>T	I510F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include premPS and AlphaMissense‑Optimized, whereas the majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Foldetta) predict a pathogenic impact; Rosetta remains uncertain. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-8.185	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	4.66	Destabilizing	0.7	1.38	Ambiguous	3.02	Destabilizing	0.50	Likely Benign	0.692	Likely Pathogenic	-2.64	Deleterious	0.991	Probably Damaging	0.854	Possibly Damaging	-1.14	Pathogenic	0.01	Affected			0.0552	0.1794		1	0	-1.7	34.02
c.1529T>A	I510N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510N is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic impact. Based on the uniform predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-12.784	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	3.09	Destabilizing	0.1	3.00	Destabilizing	3.05	Destabilizing	2.08	Destabilizing	0.925	Likely Pathogenic	-5.62	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.45	Pathogenic	0.00	Affected			0.0761	0.0270		-2	-3	-8.0	0.94
c.1529T>C	I510T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Foldetta—classify the variant as pathogenic, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-9.993	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	3.08	Destabilizing	0.2	1.99	Ambiguous	2.54	Destabilizing	1.95	Destabilizing	0.914	Likely Pathogenic	-3.63	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.43	Pathogenic	0.00	Affected			0.0960	0.0440		0	-1	-5.2	-12.05
c.1529T>G	I510S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510S is listed in ClinVar as Pathogenic (ClinVar ID 449946.0) and is not reported in gnomAD. Prediction tools that assess the variant’s effect all converge on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. No tool predicts a benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000					Likely Pathogenic		1				-11.661	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous	4.00	Destabilizing	0.1	3.78	Destabilizing	3.89	Destabilizing	2.34	Destabilizing	0.926	Likely Pathogenic	-4.63	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.44	Pathogenic	0.00	Affected	3.37	35	0.2395	0.0858		-1	-2	-5.3	-26.08	201.4	45.9	-0.4	0.2	0.0	0.3							X	Potentially Pathogenic	Ile510 is located in the middle of an α-helix (res. Gly502-Tyr518) within the inter-helix space of three helices (res. Gly502-Tyr518, Ala533-Val560, and res. Glu582-Met603). In the WT simulations, the sec-butyl side chain of Ile510 hydrophobically packs with other residues in the inter-helix space (e.g., Leu506, Leu610, Ile514, Ile602, Leu598). In the variant simulations, the hydroxyl group of Ser510 forms a hydrogen bond with the backbone atoms of Leu506 and Gly511 in the same α-helix, which could further weaken the α-helix integrity. This α-helix already shows weakness in the WT simulations due to Gly511. Although the simulations do not show large-scale effects, the residue swap could have a substantial impact due to the fundamental role of hydrophobic packing during protein folding.
c.152T>A	I51N 2D AIThe SynGAP1 missense variant I51N is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available output for this variant. Consequently, the evidence is split evenly between benign and pathogenic predictions, with no decisive support from the most accurate methods. The variant is therefore inconclusive; it is not contradicted by any ClinVar record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-9.287	Likely Pathogenic	0.909	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-1.77	Neutral	0.704	Possibly Damaging	0.272	Benign	4.13	Benign	0.00	Affected			0.1005	0.0769		-2	-3	-8.0	0.94
c.152T>C	I51T 2D AIThe SynGAP1 missense variant I51T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, AlphaMissense‑Optimized remains Uncertain, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-5.861	Likely Benign	0.881	Likely Pathogenic	Ambiguous										0.135	Likely Benign	-1.07	Neutral	0.084	Benign	0.050	Benign	4.16	Benign	0.00	Affected			0.1180	0.1265		0	-1	-5.2	-12.05
c.1525G>C	A509P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a pathogenic impact. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status (no report). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-13.234	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	5.82	Destabilizing	0.6	7.70	Destabilizing	6.76	Destabilizing	1.13	Destabilizing	0.884	Likely Pathogenic	-4.15	Deleterious	0.987	Probably Damaging	0.844	Possibly Damaging	-1.39	Pathogenic	0.01	Affected			0.1940	0.4570		1	-1	-3.4	26.04
c.1525G>A	A509T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain and therefore unavailable for interpretation. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-8.961	Likely Pathogenic	0.171	Likely Benign	Likely Benign	0.95	Ambiguous	0.4	0.61	Ambiguous	0.78	Ambiguous	0.04	Likely Benign	0.360	Likely Benign	-2.15	Neutral	0.031	Benign	0.058	Benign	-1.25	Pathogenic	0.32	Tolerated			0.1344	0.5593		1	0	-2.5	30.03
c.151A>T	I51F 2D AIThe SynGAP1 missense variant I51F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for I51F, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-5.687	Likely Benign	0.526	Ambiguous	Likely Benign										0.114	Likely Benign	-0.87	Neutral	0.099	Benign	0.039	Benign	4.13	Benign	0.00	Affected			0.0565	0.3070		1	0	-1.7	34.02
c.1520A>C	K507T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K507T missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifying it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain result. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the absence of a ClinVar classification. **The variant is most likely pathogenic based on the current predictive evidence.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.244	Likely Pathogenic	0.468	Ambiguous	Likely Benign	0.82	Ambiguous	0.1	0.31	Likely Benign	0.57	Ambiguous	0.78	Ambiguous	0.724	Likely Pathogenic	-2.86	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.55	Pathogenic	0.12	Tolerated			0.1501	0.2451		0	-1	3.2	-27.07
c.1520A>T	K507M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K507M missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, more tools (8) predict pathogenicity than benign (5), and the high‑accuracy consensus leans toward pathogenicity. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-9.548	Likely Pathogenic	0.576	Likely Pathogenic	Likely Benign	0.12	Likely Benign	0.1	-0.74	Ambiguous	-0.31	Likely Benign	-0.22	Likely Benign	0.850	Likely Pathogenic	-2.39	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	-1.63	Pathogenic	0.03	Affected			0.0783	0.2251		0	-1	5.8	3.02
c.1521G>C	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas a pathogenic signal is reported by REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta’s stability prediction is unavailable. Overall, the majority of tools (10 out of 14 with definitive calls) predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1521G>T	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict a pathogenic effect comprise REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (10 pathogenic vs. 4 benign) predict a deleterious impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1522G>A	D508N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508N missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, FATHMM, AlphaMissense‑Optimized) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b). Three tools remain uncertain (Rosetta, Foldetta, AlphaMissense‑Default). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized classifies the change as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—returns a pathogenic verdict; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an inconclusive result. Because the consensus of the high‑accuracy methods is split, the overall prediction is ambiguous, but the balance of evidence leans toward pathogenicity. This assessment does not contradict ClinVar, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-9.909	Likely Pathogenic	0.411	Ambiguous	Likely Benign	0.11	Likely Benign	0.1	1.24	Ambiguous	0.68	Ambiguous	-0.12	Likely Benign	0.265	Likely Benign	-4.62	Deleterious	0.870	Possibly Damaging	0.615	Possibly Damaging	3.32	Benign	0.04	Affected			0.1577	0.4599		2	1	0.0	-0.98
c.1522G>C	D508H 2D AISynGAP1 D508H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show an even split: benign calls come from REVEL, FoldX, premPS, SIFT, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments give a pathogenic consensus from the SGM method (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), an uncertain outcome from AlphaMissense‑Optimized, and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). Overall, the balance of evidence leans toward pathogenicity, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-12.074	Likely Pathogenic	0.849	Likely Pathogenic	Ambiguous	0.15	Likely Benign	0.4	0.97	Ambiguous	0.56	Ambiguous	-0.14	Likely Benign	0.336	Likely Benign	-6.38	Deleterious	0.998	Probably Damaging	0.919	Probably Damaging	3.26	Benign	0.06	Tolerated			0.1804	0.5096		1	-1	0.3	22.05
c.1522G>T	D508Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508Y missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta predicting a benign outcome. Overall, the majority of evidence (seven pathogenic vs. five benign) points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-12.917	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	-0.53	Ambiguous	0.2	0.72	Ambiguous	0.10	Likely Benign	0.06	Likely Benign	0.363	Likely Benign	-8.37	Deleterious	1.000	Probably Damaging	0.965	Probably Damaging	3.26	Benign	0.01	Affected			0.0908	0.4736		-4	-3	2.2	48.09
c.1523A>C	D508A 2D 3DClick to see structure in 3D Viewer AISynGAP1 D508A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give a split result: AlphaMissense‑Optimized predicts benign, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. No prediction or stability result is missing; all available outputs are considered. Overall, the predictions are evenly divided between benign and pathogenic, with no clear consensus. Therefore, the variant is inconclusive; it is not contradictory to the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-11.434	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	-0.18	Likely Benign	0.2	1.84	Ambiguous	0.83	Ambiguous	0.09	Likely Benign	0.339	Likely Benign	-7.37	Deleterious	0.988	Probably Damaging	0.762	Possibly Damaging	3.37	Benign	0.06	Tolerated			0.3758	0.4241		0	-2	5.3	-44.01
c.1523A>G	D508G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. FoldX‑MD is inconclusive and is treated as unavailable. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and a pathogenic prediction from Foldetta. Overall, the majority of evidence, including the high‑accuracy tools, supports a pathogenic effect. This conclusion does not contradict ClinVar, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-8.478	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.2	3.20	Destabilizing	2.04	Destabilizing	0.13	Likely Benign	0.368	Likely Benign	-6.61	Deleterious	0.997	Probably Damaging	0.933	Probably Damaging	3.30	Benign	0.07	Tolerated			0.3821	0.4528		1	-1	3.1	-58.04
c.1523A>T	D508V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508V missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (a folding‑stability method combining FoldX‑MD and Rosetta outputs) as benign. With seven benign versus six pathogenic calls and two of the three high‑accuracy tools supporting benign, the variant is most likely benign. This conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-13.529	Likely Pathogenic	0.691	Likely Pathogenic	Likely Benign	0.07	Likely Benign	0.1	0.66	Ambiguous	0.37	Likely Benign	0.07	Likely Benign	0.381	Likely Benign	-8.37	Deleterious	0.985	Probably Damaging	0.895	Possibly Damaging	3.27	Benign	0.08	Tolerated			0.1050	0.4604		-2	-3	7.7	-15.96
c.1524T>G	D508E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) all classify the change as benign. Only PROVEAN predicts a pathogenic outcome, while Rosetta and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign stability. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-5.959	Likely Benign	0.242	Likely Benign	Likely Benign	-0.39	Likely Benign	0.1	0.99	Ambiguous	0.30	Likely Benign	0.59	Ambiguous	0.118	Likely Benign	-3.16	Deleterious	0.005	Benign	0.006	Benign	3.43	Benign	0.20	Tolerated	3.37	35	0.1766	0.4304		2	3	0.0	14.03
c.152T>G	I51S 2D AIThe SynGAP1 missense variant I51S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The remaining tools, ESM1b and AlphaMissense‑Optimized, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (2 benign vs. 1 pathogenic vote). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-7.603	In-Between	0.879	Likely Pathogenic	Ambiguous										0.220	Likely Benign	-1.39	Neutral	0.182	Benign	0.099	Benign	4.15	Benign	0.00	Affected			0.3142	0.0957		-1	-2	-5.3	-26.08
c.1530T>G	I510M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I510M missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign impact include PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (benign), ESM1b (uncertain), FATHMM (pathogenic), and PROVEAN (benign)—also favors benign. Foldetta, a protein‑folding stability method, yielded an uncertain outcome. Taken together, the consensus of the most reliable predictors indicates a benign effect. This conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-7.988	In-Between	0.235	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.61	Ambiguous	1.09	Ambiguous	0.55	Ambiguous	0.532	Likely Pathogenic	-0.97	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	-1.42	Pathogenic	0.02	Affected			0.0674	0.1789		2	1	-2.6	18.03
c.1531G>A	G511R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G511R is listed in ClinVar as Pathogenic (ClinVar ID 1774641.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Stability calculations from FoldX and Rosetta are uncertain, and premPS is unavailable. Overall, the majority of evidence points to a pathogenic 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 Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000					Likely Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	0.416	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	0.1307	0.4104		-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1537T>C	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.674	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1312G>T	A438S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A438S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as benign. The only inconclusive results come from Rosetta and premPS, which are listed as uncertain. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Overall, the evidence strongly supports a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.147574	Structured	0.290154	Uncertain	0.929	0.293	0.000											-6.085	Likely Benign	0.105	Likely Benign	Likely Benign	0.30	Likely Benign	0.0	0.62	Ambiguous	0.46	Likely Benign	0.68	Ambiguous	0.012	Likely Benign	-1.27	Neutral	0.042	Benign	0.035	Benign	4.14	Benign	0.15	Tolerated			0.2143	0.3995		1	1	-2.6	16.00
c.1537T>G	F513V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.675	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.54	Destabilizing	0.4	2.68	Destabilizing	3.11	Destabilizing	1.13	Destabilizing	0.799	Likely Pathogenic	-6.70	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.44	Tolerated			0.1656	0.1583		-1	-1	1.4	-48.04
c.1312G>C	A438P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A438P missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas those that predict a pathogenic impact are FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv), SIFT, and AlphaMissense‑Default; premPS and ESM1b are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as pathogenic. Overall, six tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus is split, but the majority of evidence points toward a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.147574	Structured	0.290154	Uncertain	0.929	0.293	0.000											-7.955	In-Between	0.721	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.1	6.36	Destabilizing	4.29	Destabilizing	0.83	Ambiguous	0.158	Likely Benign	-2.46	Neutral	0.815	Possibly Damaging	0.137	Benign	4.09	Benign	0.05	Affected			0.1624	0.4150		1	-1	-3.4	26.04
c.1538T>A	F513Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenicity. Stability‑based methods (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as uncertain. With 10 of 12 evaluated tools indicating pathogenicity and no conflicting ClinVar annotation, the variant is most likely pathogenic, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.022	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	1.09	Ambiguous	0.2	1.03	Ambiguous	1.06	Ambiguous	1.09	Destabilizing	0.791	Likely Pathogenic	-2.92	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.39	Pathogenic	0.07	Tolerated			0.1046	0.1087		7	3	-4.1	16.00
c.1538T>C	F513S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, whereas all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-12.172	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.21	Destabilizing	0.4	4.43	Destabilizing	4.32	Destabilizing	2.25	Destabilizing	0.917	Likely Pathogenic	-7.75	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.27	Pathogenic	0.10	Tolerated			0.3864	0.0200		-3	-2	-3.6	-60.10
c.1310C>T	P437L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta are uncertain. Taken together, the majority of evidence points toward a pathogenic impact for P437L, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.554	Likely Pathogenic	0.787	Likely Pathogenic	Ambiguous	1.10	Ambiguous	0.0	-3.52	Stabilizing	-1.21	Ambiguous	0.35	Likely Benign	0.324	Likely Benign	-8.48	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.67	Benign	0.04	Affected			0.2228	0.6354		-3	-3	5.4	16.04
c.1538T>G	F513C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513C is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also labels it pathogenic. Based on the uniform predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-11.389	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.3	4.20	Destabilizing	4.06	Destabilizing	1.64	Destabilizing	0.919	Likely Pathogenic	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.03	Affected			0.2384	0.0783		-4	-2	-0.3	-44.04
c.1539C>A	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1310C>G	P437R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P437R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the majority of tools indicating pathogenicity and the high‑accuracy consensus leaning toward pathogenic, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.094	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-3.52	Stabilizing	-1.59	Ambiguous	0.61	Ambiguous	0.461	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.51	Benign	0.03	Affected			0.1448	0.2846		0	-2	-2.9	59.07
c.1539C>G	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F513L missense variant has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict pathogenicity. 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, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is inconclusive and therefore not considered evidence. FoldX and Rosetta predictions are uncertain and treated as unavailable. Overall, the preponderance of evidence indicates that F513L is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1310C>A	P437H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the balance of evidence favors a pathogenic classification for P437H, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.496	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	1.19	Ambiguous	0.0	-3.28	Stabilizing	-1.05	Ambiguous	0.31	Likely Benign	0.343	Likely Benign	-7.75	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.44	Benign	0.01	Affected			0.1819	0.4328		0	-2	-1.6	40.02
c.1537T>A	F513I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513I is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely converge on a deleterious effect: SIFT is the sole benign caller, whereas REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. Grouping by consensus, the single benign prediction (SIFT) is outweighed by the 13 pathogenic calls. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-12.003	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.42	Destabilizing	0.4	2.18	Destabilizing	2.80	Destabilizing	1.12	Destabilizing	0.766	Likely Pathogenic	-5.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.24	Pathogenic	0.22	Tolerated			0.1473	0.1766		1	0	1.7	-34.02
c.1536A>T	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E512D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Across the broad panel of in‑silico predictors, the majority (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as benign, whereas only ESM1b predicts it as pathogenic. The high‑accuracy tools give a consistent benign signal: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the evidence strongly supports a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
c.1531G>C	G511R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511R is listed in ClinVar (ID 452818.0) as Pathogenic 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, 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 outputs) as Uncertain, which is treated as unavailable evidence. Overall, the majority of available predictions support a pathogenic impact, aligning with the ClinVar classification. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000					Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	0.415	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	0.1307	0.4104		-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1532G>A	G511E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000											-12.263	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.17	Destabilizing	0.2	2.62	Destabilizing	2.40	Destabilizing	1.15	Destabilizing	0.479	Likely Benign	-7.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.24	Benign	0.02	Affected			0.1882	0.4240		0	-2	-3.1	72.06
c.1532G>C	G511A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000											-9.621	Likely Pathogenic	0.844	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.2	0.25	Likely Benign	0.53	Ambiguous	0.55	Ambiguous	0.275	Likely Benign	-5.73	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.23	Benign	0.02	Affected			0.3793	0.2778		1	0	2.2	14.03
c.1532G>T	G511V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511V is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no classification for G511V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000											-11.738	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	3.47	Destabilizing	0.2	0.79	Ambiguous	2.13	Destabilizing	0.65	Ambiguous	0.540	Likely Pathogenic	-8.71	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.16	Benign	0.01	Affected			0.1557	0.3019		-1	-3	4.6	42.08
c.1534G>A	E512K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512K missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, premPS, and Foldetta, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, seven tools predict pathogenicity versus six predicting benignity, with one uncertain result. Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-13.927	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.1	0.63	Ambiguous	0.40	Likely Benign	-0.03	Likely Benign	0.344	Likely Benign	-3.85	Deleterious	0.962	Probably Damaging	0.658	Possibly Damaging	3.32	Benign	0.06	Tolerated			0.2844	0.4776		0	1	-0.4	-0.94
c.1534G>C	E512Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512Q missense change is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Because the variant is absent from ClinVar and gnomAD, there is no external evidence to contradict the computational predictions. Overall, the balance of high‑confidence tools leans toward a pathogenic interpretation, though the presence of an equal number of benign predictions indicates that the evidence remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-9.964	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	0.09	Likely Benign	0.1	0.42	Likely Benign	0.26	Likely Benign	0.00	Likely Benign	0.283	Likely Benign	-2.86	Deleterious	0.947	Possibly Damaging	0.706	Possibly Damaging	3.32	Benign	0.14	Tolerated			0.1523	0.4815		2	2	0.0	-0.98
c.1535A>C	E512A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-10.979	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.97	Ambiguous	0.71	Ambiguous	0.04	Likely Benign	0.309	Likely Benign	-5.71	Deleterious	0.987	Probably Damaging	0.937	Probably Damaging	3.31	Benign	0.12	Tolerated			0.4293	0.5162		0	-1	5.3	-58.04
c.1535A>G	E512G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512G is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E512G, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-11.996	Likely Pathogenic	0.817	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.1	1.84	Ambiguous	1.35	Ambiguous	0.17	Likely Benign	0.381	Likely Benign	-6.46	Deleterious	0.997	Probably Damaging	0.915	Probably Damaging	3.30	Benign	0.02	Affected			0.3262	0.4185		0	-2	3.1	-72.06
c.1313C>G	A438G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A438G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only PROVEAN predicts a pathogenic outcome. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for A438G, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.147574	Structured	0.290154	Uncertain	0.929	0.293	0.000											-5.790	Likely Benign	0.182	Likely Benign	Likely Benign	1.08	Ambiguous	0.1	1.78	Ambiguous	1.43	Ambiguous	0.80	Ambiguous	0.034	Likely Benign	-2.51	Deleterious	0.247	Benign	0.037	Benign	4.12	Benign	0.11	Tolerated			0.1788	0.2719		1	0	-2.2	-14.03
c.1535A>T	E512V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-14.011	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	0.72	Ambiguous	0.1	1.00	Ambiguous	0.86	Ambiguous	0.14	Likely Benign	0.439	Likely Benign	-6.71	Deleterious	0.989	Probably Damaging	0.854	Possibly Damaging	3.23	Benign	0.01	Affected			0.0994	0.4884		-2	-2	7.7	-29.98
c.1536A>C	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512D is not reported in ClinVar or gnomAD. Across a broad panel of in silico predictors, the majority indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only the ESM1b model assigns a pathogenic label, while Rosetta and Foldetta provide uncertain results. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains inconclusive. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
c.1313C>A	A438D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A438D missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments indicate that AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is also inconclusive. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Thus, based on the available predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.147574	Structured	0.290154	Uncertain	0.929	0.293	0.000											-7.410	In-Between	0.808	Likely Pathogenic	Ambiguous	1.60	Ambiguous	0.1	0.70	Ambiguous	1.15	Ambiguous	0.92	Ambiguous	0.175	Likely Benign	-3.07	Deleterious	0.859	Possibly Damaging	0.124	Benign	4.10	Benign	0.04	Affected			0.1490	0.1941		0	-2	-5.3	44.01
c.153C>G	I51M 2D AIThe SynGAP1 missense variant I51M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, the I51M substitution is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-4.732	Likely Benign	0.381	Ambiguous	Likely Benign										0.093	Likely Benign	-0.27	Neutral	0.099	Benign	0.075	Benign	4.13	Benign	0.00	Affected			0.0764	0.3281		2	1	-2.6	18.03
c.1288A>T	M430L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, FoldX, Rosetta, PolyPhen‑2 (HumDiv and HumVar), SIFT, and REVEL; no tool predicts pathogenicity. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all available evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-5.873	Likely Benign	0.104	Likely Benign	Likely Benign	0.33	Likely Benign	0.1	-0.10	Likely Benign	0.12	Likely Benign	0.72	Ambiguous	0.107	Likely Benign	-1.07	Neutral	0.028	Benign	0.004	Benign	3.69	Benign	0.66	Tolerated			0.1767	0.5067		4	2	1.9	-18.03
c.1281T>G	H427Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect for H427Q. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-5.858	Likely Benign	0.367	Ambiguous	Likely Benign	0.77	Ambiguous	0.1	0.62	Ambiguous	0.70	Ambiguous	0.73	Ambiguous	0.142	Likely Benign	-2.41	Neutral	0.864	Possibly Damaging	0.088	Benign	3.52	Benign	0.02	Affected			0.1556	0.3382		3	0	-0.3	-9.01
c.1281T>A	H427Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect for H427Q. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-5.858	Likely Benign	0.367	Ambiguous	Likely Benign	0.77	Ambiguous	0.1	0.62	Ambiguous	0.70	Ambiguous	0.73	Ambiguous	0.142	Likely Benign	-2.41	Neutral	0.864	Possibly Damaging	0.088	Benign	3.52	Benign	0.02	Affected			0.1556	0.3382		3	0	-0.3	-9.01
c.1280A>T	H427L 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: nine tools (REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized) predict a benign effect, while five tools (SGM‑Consensus, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy methods provide a more focused view: AlphaMissense‑Optimized indicates a benign outcome; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, remains pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Taken together, the majority of evidence supports a benign impact for H427L, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-9.691	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	-0.17	Likely Benign	0.0	0.05	Likely Benign	-0.06	Likely Benign	0.31	Likely Benign	0.272	Likely Benign	-5.38	Deleterious	0.299	Benign	0.033	Benign	3.42	Benign	0.01	Affected			0.0942	0.4953		-2	-3	7.0	-23.98
c.1574A>C	E525A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E525A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, premPS, and FATHMM, whereas the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic classification for E525A, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-12.627	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.6	-0.62	Ambiguous	0.31	Likely Benign	0.09	Likely Benign	0.680	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.00	Affected			0.3554	0.3960		0	-1	5.3	-58.04
c.1574A>G	E525G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—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)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns a pathogenic score, the SGM‑Consensus also indicates pathogenicity, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Taken together, the overwhelming majority of evidence points to a pathogenic impact for E525G. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.181	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.6	0.90	Ambiguous	1.31	Ambiguous	0.78	Ambiguous	0.691	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.00	Affected			0.2947	0.3886		0	-2	3.1	-72.06
c.1574A>T	E525V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Foldetta, premPS, and FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome; FoldX and Rosetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for E525V, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.622	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	1.10	Ambiguous	0.7	-0.69	Ambiguous	0.21	Likely Benign	0.00	Likely Benign	0.683	Likely Pathogenic	-6.96	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	2.66	Benign	0.00	Affected			0.0721	0.4946		-2	-2	7.7	-29.98
c.1575G>C	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are therefore not used to weigh the overall assessment. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for E525D. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1280A>C	H427P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools are uncertain: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate a pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification for H427P, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-11.098	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	4.74	Destabilizing	0.1	7.61	Destabilizing	6.18	Destabilizing	0.68	Ambiguous	0.324	Likely Benign	-4.22	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.51	Benign	0.01	Affected			0.2061	0.3442		0	-2	1.6	-40.02
c.1575G>T	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the balance of evidence (nine pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.127G>T	G43C 2D AIThe SynGAP1 missense variant G43C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431462	Uncertain	0.396	0.762	0.375											-4.599	Likely Benign	0.109	Likely Benign	Likely Benign										0.077	Likely Benign	-0.90	Neutral	0.987	Probably Damaging	0.750	Possibly Damaging	4.18	Benign	0.00	Affected			0.1445	0.3438		-3	-3	2.9	46.09
c.127G>C	G43R 2D AIThe SynGAP1 missense variant G43R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for G43R, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431462	Uncertain	0.396	0.762	0.375											-2.104	Likely Benign	0.266	Likely Benign	Likely Benign										0.085	Likely Benign	-1.26	Neutral	0.870	Possibly Damaging	0.500	Possibly Damaging	4.22	Benign	0.00	Affected			0.1025	0.3645		-3	-2	-4.1	99.14
c.1279C>T	H427Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H427Y missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar, as well as the SGM‑Consensus “Likely Benign” call. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and SIFT. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta)—all uniformly indicate a benign effect. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-6.824	Likely Benign	0.328	Likely Benign	Likely Benign	-0.08	Likely Benign	0.0	-0.37	Likely Benign	-0.23	Likely Benign	0.18	Likely Benign	0.180	Likely Benign	-3.47	Deleterious	0.815	Possibly Damaging	0.073	Benign	3.44	Benign	0.01	Affected			0.0958	0.4029		0	2	1.9	26.03
c.1282T>A	Y428N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, which classifies the change as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-12.164	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	2.34	Destabilizing	0.0	3.81	Destabilizing	3.08	Destabilizing	1.85	Destabilizing	0.533	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.03	Affected			0.2607	0.0971		-2	-2	-2.2	-49.07
c.1282T>G	Y428D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y428D is not reported in ClinVar and is absent from gnomAD. Across a broad panel of in silico predictors, 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a deleterious effect, whereas only FATHMM classifies it as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic effect. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-13.473	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.24	Destabilizing	0.0	4.19	Destabilizing	3.72	Destabilizing	1.64	Destabilizing	0.554	Likely Pathogenic	-9.55	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.50	Benign	0.01	Affected			0.4458	0.1003		-4	-3	-2.2	-48.09
c.1288A>G	M430V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated changes. Only polyPhen‑2 HumDiv flags it as pathogenic, while the SGM‑Consensus score is Likely Benign. Stability‑based methods are inconclusive: FoldX and premPS return Uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports Uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta remains Uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-3.555	Likely Benign	0.091	Likely Benign	Likely Benign	1.48	Ambiguous	0.1	-0.23	Likely Benign	0.63	Ambiguous	0.87	Ambiguous	0.103	Likely Benign	-1.35	Neutral	0.918	Possibly Damaging	0.185	Benign	3.53	Benign	0.51	Tolerated			0.3397	0.4953		2	1	2.3	-32.06
c.1288A>C	M430L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, FoldX, Rosetta, PolyPhen‑2 (HumDiv and HumVar), SIFT, and REVEL; no tool predicts pathogenicity. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all available evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-5.873	Likely Benign	0.104	Likely Benign	Likely Benign	0.33	Likely Benign	0.1	-0.10	Likely Benign	0.12	Likely Benign	0.72	Ambiguous	0.107	Likely Benign	-1.07	Neutral	0.028	Benign	0.004	Benign	3.69	Benign	0.66	Tolerated			0.1767	0.5067		4	2	1.9	-18.03
c.1571G>C	C524S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 C524S variant has no ClinVar entry and is not present in gnomAD. Prediction tools that agree on a benign effect are none; those that predict pathogenicity include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta returned inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.174	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.1	1.55	Ambiguous	1.18	Ambiguous	1.58	Destabilizing	0.904	Likely Pathogenic	-9.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.38	Pathogenic	0.00	Affected	3.37	35	0.5362	0.1848	Weaken	-1	0	-3.3	-16.06
c.1571G>T	C524F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524F is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized reports pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-12.145	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.18	Destabilizing	1.4	5.20	Destabilizing	3.69	Destabilizing	-0.04	Likely Benign	0.831	Likely Pathogenic	-10.94	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.05	Affected			0.1678	0.4259		-4	-2	0.3	44.04
c.1572C>G	C524W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524W is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: benign predictions are absent, while pathogenic predictions are made by REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-12.351	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.03	Destabilizing	1.2	9.88	Destabilizing	6.46	Destabilizing	0.93	Ambiguous	0.675	Likely Pathogenic	-10.94	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.41	Pathogenic	0.00	Affected			0.1953	0.3920		-8	-2	-3.4	83.07
c.1286G>T	R429L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). 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, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. No contradictory evidence is present from ClinVar or gnomAD. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-6.495	Likely Benign	0.408	Ambiguous	Likely Benign	-0.05	Likely Benign	0.1	0.06	Likely Benign	0.01	Likely Benign	-0.12	Likely Benign	0.241	Likely Benign	-1.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.59	Benign	0.37	Tolerated			0.1555	0.4025		-3	-2	8.3	-43.03
c.1286G>C	R429P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; AlphaMissense‑Default and FoldX are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools and the high‑accuracy methods favor a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-9.771	Likely Pathogenic	0.556	Ambiguous	Likely Benign	1.53	Ambiguous	0.2	5.13	Destabilizing	3.33	Destabilizing	1.01	Destabilizing	0.265	Likely Benign	-2.89	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.25	Tolerated			0.1881	0.3790		0	-2	2.9	-59.07
c.1573G>C	E525Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely disagree: benign predictions come from Rosetta, Foldetta, and FATHMM, while pathogenic predictions are returned by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.722	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	1.05	Ambiguous	0.7	-0.11	Likely Benign	0.47	Likely Benign	0.84	Ambiguous	0.516	Likely Pathogenic	-2.98	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.68	Benign	0.00	Affected			0.1173	0.3962		2	2	0.0	-0.98
c.1285C>G	R429G 2D 3DClick to see structure in 3D Viewer AISynGAP1 R429G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta’s stability analysis is uncertain. No evidence from FoldX or Rosetta is available. Overall, the predictions are evenly split, with no clear consensus. The variant is most likely of uncertain significance; it is not contradicted by ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-9.157	Likely Pathogenic	0.333	Likely Benign	Likely Benign	1.58	Ambiguous	0.0	1.68	Ambiguous	1.63	Ambiguous	1.21	Destabilizing	0.257	Likely Benign	-3.37	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.43	Benign	0.34	Tolerated			0.2888	0.2717		-3	-2	4.1	-99.14
c.1283A>T	Y428F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as unavailable. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a pathogenic SGM Consensus and a benign AlphaMissense‑Optimized—suggests that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.464	Likely Pathogenic	0.530	Ambiguous	Likely Benign	0.82	Ambiguous	0.1	0.52	Ambiguous	0.67	Ambiguous	0.89	Ambiguous	0.366	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.41	Benign	0.04	Affected			0.2719	0.3146		7	3	4.1	-16.00
c.1283A>G	Y428C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus result as “Likely Pathogenic,” Foldetta predicts a destabilizing, pathogenic effect, while AlphaMissense‑Optimized is uncertain. No prediction or stability result is missing; the only inconclusive outcome is the AlphaMissense‑Optimized score. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-11.312	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	2.82	Destabilizing	0.0	2.99	Destabilizing	2.91	Destabilizing	2.02	Destabilizing	0.454	Likely Benign	-8.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.39	Benign	0.01	Affected			0.3322	0.2220		0	-2	3.8	-60.04
c.1283A>C	Y428S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. All other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.936	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	3.00	Destabilizing	0.0	3.42	Destabilizing	3.21	Destabilizing	2.00	Destabilizing	0.505	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.4623	0.2352		-3	-2	0.5	-76.10
c.1279C>G	H427D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H427D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No evidence from the available tools suggests pathogenicity, and the absence of a ClinVar classification means there is no contradiction. Therefore, based on the current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-3.684	Likely Benign	0.500	Ambiguous	Likely Benign	0.76	Ambiguous	0.1	1.26	Ambiguous	1.01	Ambiguous	0.10	Likely Benign	0.163	Likely Benign	-1.43	Neutral	0.677	Possibly Damaging	0.236	Benign	3.58	Benign	0.12	Tolerated			0.2241	0.1678		1	-1	-0.3	-22.05
c.1279C>A	H427N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign outcome. With all available evidence pointing to a neutral effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											1.162	Likely Benign	0.045	Likely Benign	Likely Benign	-0.11	Likely Benign	0.1	0.39	Likely Benign	0.14	Likely Benign	-0.48	Likely Benign	0.100	Likely Benign	1.63	Neutral	0.010	Benign	0.006	Benign	3.62	Benign	0.46	Tolerated			0.1507	0.2418		2	1	-0.3	-23.04
c.1278C>G	N426K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426K is located in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect on protein stability. Overall, the majority of predictions lean toward pathogenicity, with a split in the most reliable methods. Therefore, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1580A>G	D527G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D527G is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools cluster into two groups: the single benign prediction comes from premPS, while all other evaluated algorithms—SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—indicate pathogenicity. FoldX is uncertain and therefore not counted as evidence for either side. High‑accuracy methods reinforce the pathogenic assessment: AlphaMissense‑Optimized predicts 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 contradictory evidence exists in ClinVar. **Thus, the variant is most likely pathogenic based on the collective predictions, with no ClinVar status to contradict this assessment.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-15.177	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	1.0	4.22	Destabilizing	2.97	Destabilizing	0.33	Likely Benign	0.933	Likely Pathogenic	-6.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-2.39	Pathogenic	0.01	Affected			0.2847	0.4366		1	-1	3.1	-58.04
c.1580A>T	D527V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527V missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that are uncertain (FoldX, Rosetta, Foldetta, premPS) provide no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, while Foldetta remains uncertain. Overall, the majority of reliable predictors classify the variant as pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-16.844	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.71	Ambiguous	0.7	0.84	Ambiguous	0.78	Ambiguous	-0.55	Ambiguous	0.938	Likely Pathogenic	-8.78	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-2.40	Pathogenic	0.00	Affected			0.0659	0.3984		-2	-3	7.7	-15.96
c.1581C>A	D527E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527E missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, whereas only FoldX and premPS predict a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains Likely Pathogenic. Overall, the preponderance of evidence points to a pathogenic impact, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-11.125	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.8	2.29	Destabilizing	1.33	Ambiguous	0.50	Likely Benign	0.740	Likely Pathogenic	-3.74	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-2.31	Pathogenic	0.02	Affected			0.1103	0.3428		3	2	0.0	14.03
c.1277A>G	N426S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The high‑accuracy AlphaMissense‑Optimized score is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and the Foldetta stability assessment is inconclusive. No evidence from FoldX or Rosetta is available. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-5.215	Likely Benign	0.081	Likely Benign	Likely Benign	0.81	Ambiguous	0.0	0.52	Ambiguous	0.67	Ambiguous	0.03	Likely Benign	0.131	Likely Benign	-2.37	Neutral	0.998	Probably Damaging	0.921	Probably Damaging	3.47	Benign	0.33	Tolerated			0.2224	0.3188		1	1	2.7	-27.03
c.1581C>G	D527E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527E missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, whereas only FoldX and premPS predict a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains Likely Pathogenic. Overall, the preponderance of evidence points to a pathogenic impact, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-11.125	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.8	2.29	Destabilizing	1.33	Ambiguous	0.50	Likely Benign	0.740	Likely Pathogenic	-3.74	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-2.31	Pathogenic	0.02	Affected			0.1103	0.3428		3	2	0.0	14.03
c.1582C>A	P528T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-13.782	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.3	1.01	Ambiguous	1.53	Ambiguous	0.66	Ambiguous	0.673	Likely Pathogenic	-7.69	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1367	0.4360		0	-1	0.9	3.99
c.1582C>G	P528A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized, while the remaining pathogenic‑predicting tools are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, Foldetta, premPS) are uncertain. High‑accuracy methods give AlphaMissense‑Optimized a benign score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) a pathogenic prediction, and Foldetta an uncertain result. Overall, the majority of evidence points to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-11.562	Likely Pathogenic	0.607	Likely Pathogenic	Likely Benign	1.57	Ambiguous	0.1	1.49	Ambiguous	1.53	Ambiguous	0.69	Ambiguous	0.548	Likely Pathogenic	-7.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.52	Benign	0.01	Affected			0.3146	0.3914		1	-1	3.4	-26.04
c.1582C>T	P528S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528S missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only FATHMM predicts a benign outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. No folding‑stability metrics (FoldX, Rosetta, premPS) provide definitive evidence. Overall, the preponderance of pathogenic predictions suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-11.729	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	1.88	Ambiguous	0.1	1.28	Ambiguous	1.58	Ambiguous	0.80	Ambiguous	0.617	Likely Pathogenic	-7.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.52	Benign	0.01	Affected			0.3115	0.3982		1	-1	0.8	-10.04
c.1583C>A	P528H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely pathogenic. No tool predicts a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain or inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar entry; there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-15.365	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	1.93	Ambiguous	0.1	0.74	Ambiguous	1.34	Ambiguous	0.61	Ambiguous	0.565	Likely Pathogenic	-8.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.47	Pathogenic	0.00	Affected			0.1434	0.3523		0	-2	-1.6	40.02
c.1583C>G	P528R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528R missense variant is not reported in ClinVar and is absent from gnomAD. No in silico predictor classifies it as benign; the following tools predict pathogenicity: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are uncertain or inconclusive (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-16.367	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.76	Ambiguous	0.4	0.67	Ambiguous	0.72	Ambiguous	0.73	Ambiguous	0.615	Likely Pathogenic	-8.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.49	Pathogenic	0.01	Affected			0.1261	0.2543		0	-2	-2.9	59.07
c.1277A>C	N426T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change N426T lies in the GAP domain. It is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Predictions that are uncertain or inconclusive are FoldX, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta remains uncertain and is not taken as evidence. Overall, the majority of tools, including the high‑accuracy methods, predict a benign effect. This consensus does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-7.389	In-Between	0.194	Likely Benign	Likely Benign	0.84	Ambiguous	0.0	0.38	Likely Benign	0.61	Ambiguous	0.12	Likely Benign	0.126	Likely Benign	-3.14	Deleterious	0.983	Probably Damaging	0.926	Probably Damaging	3.47	Benign	0.10	Tolerated			0.1090	0.3002		0	0	2.8	-13.00
c.1276A>T	N426Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two main groups: benign predictions come from REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b. Two tools remain uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on the current predictive landscape. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-8.510	Likely Pathogenic	0.541	Ambiguous	Likely Benign	0.47	Likely Benign	0.0	-0.50	Ambiguous	-0.02	Likely Benign	0.23	Likely Benign	0.341	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.30	Benign	0.25	Tolerated			0.0578	0.3338		-2	-2	2.2	49.07
c.1580A>C	D527A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, while the remaining evaluated methods (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-15.473	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.9	1.75	Ambiguous	1.28	Ambiguous	-0.24	Likely Benign	0.929	Likely Pathogenic	-7.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.2850	0.3799		0	-2	5.3	-44.01
c.157G>T	G53W 2D AIThe SynGAP1 missense variant G53W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of available predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-11.012	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.243	Likely Benign	-1.69	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	4.08	Benign	0.00	Affected			0.0678	0.5071		-7	-2	-0.5	129.16
c.1576G>C	V526L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V526L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and SIFT, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for V526L, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-9.289	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.5	1.74	Ambiguous	1.53	Ambiguous	0.38	Likely Benign	0.643	Likely Pathogenic	-2.97	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	-1.16	Pathogenic	0.17	Tolerated			0.0754	0.3894		2	1	-0.4	14.03
c.1576G>T	V526L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V526L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and SIFT, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for V526L, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-9.289	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.5	1.74	Ambiguous	1.53	Ambiguous	0.38	Likely Benign	0.643	Likely Pathogenic	-2.97	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	-1.16	Pathogenic	0.17	Tolerated			0.0754	0.3894		2	1	-0.4	14.03
c.1577T>A	V526E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V526E is not listed in ClinVar and has no reported allele in gnomAD. In silico prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Because all available evidence points to a damaging effect and there is no conflicting ClinVar annotation or population frequency data, the variant is most likely pathogenic. This conclusion aligns with the absence of ClinVar status and gnomAD entries, indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-16.080	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	5.19	Destabilizing	0.3	5.12	Destabilizing	5.16	Destabilizing	2.32	Destabilizing	0.962	Likely Pathogenic	-5.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.46	Pathogenic	0.00	Affected			0.0766	0.1326		-2	-2	-7.7	29.98
c.1577T>C	V526A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V526A is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all agree that the variant is deleterious: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as pathogenic or likely pathogenic. No tool predicts a benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact. Based on the overwhelming consensus of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-12.055	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	2.30	Destabilizing	0.1	2.49	Destabilizing	2.40	Destabilizing	2.05	Destabilizing	0.908	Likely Pathogenic	-3.93	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.44	Pathogenic	0.00	Affected			0.2224	0.1922		0	0	-2.4	-28.05
c.1577T>G	V526G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V526G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; no tool predicts it benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. All available evidence points to a deleterious effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-15.811	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	3.21	Destabilizing	0.3	4.79	Destabilizing	4.00	Destabilizing	2.19	Destabilizing	0.935	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0.1636	0.1837		-1	-3	-4.6	-42.08
c.1579G>A	D527N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas a majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The high‑accuracy consensus methods give mixed results: AlphaMissense‑Optimized is uncertain, SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign outcome. Overall, the preponderance of evidence points toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-12.645	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.31	Likely Benign	1.0	0.09	Likely Benign	0.20	Likely Benign	0.22	Likely Benign	0.730	Likely Pathogenic	-4.87	Deleterious	0.992	Probably Damaging	0.990	Probably Damaging	-2.13	Pathogenic	0.01	Affected			0.0910	0.3754		2	1	0.0	-0.98
c.1579G>C	D527H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D527H is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX and premPS, whereas the majority of tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. Uncertain results come from Rosetta and Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as pathogenic, and Foldetta as inconclusive. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-13.334	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	1.2	1.26	Ambiguous	0.83	Ambiguous	0.49	Likely Benign	0.901	Likely Pathogenic	-6.80	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.1092	0.4346		1	-1	0.3	22.05
c.1278C>A	N426K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426K resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1579G>T	D527Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D527Y is listed in ClinVar with an uncertain significance (ClinVar ID 1698369.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: the single benign prediction from premPS versus a consensus of pathogenic predictions from the remaining 12 tools (REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Protein‑stability calculations from FoldX and Rosetta are also uncertain. Overall, the preponderance of evidence indicates that D527Y is most likely pathogenic, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000					Uncertain		1				-15.386	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	-0.77	Ambiguous	0.2	1.89	Ambiguous	0.56	Ambiguous	-0.14	Likely Benign	0.905	Likely Pathogenic	-8.79	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-2.41	Pathogenic	0.00	Affected	3.37	35	0.0554	0.4229		-4	-3	2.2	48.09	270.9	-45.7	0.1	0.1	-0.1	0.0		X						Potentially Pathogenic	Asp527 is located on an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560). In the WT simulations, the carboxylate group of the Asp527 side chain forms hydrogen bonds with the backbone atoms of loop residues (e.g., Ile529, Lys530) facing the membrane surface. In the variant simulations, Tyr527 is a bulkier residue that faces away from the loop and stacks with Phe646 in a nearby α-helix (res. Ser614-Ser668). Regardless, no negative structural effects are observed during the variant simulations. However, due to its location near the SynGAP-membrane interface, the effect of the residue swap cannot be fully addressed using the SynGAP solvent-only simulations.
c.157G>A	G53R 2D AIThe SynGAP1 missense variant G53R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic impact. Because there is no ClinVar entry to contradict this assessment, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.1277A>T	N426I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426I has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting pathogenicity, and Foldetta indicating a benign folding stability outcome. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-10.158	Likely Pathogenic	0.570	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.0	0.14	Likely Benign	0.41	Likely Benign	0.23	Likely Benign	0.216	Likely Benign	-5.71	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.31	Benign	0.09	Tolerated			0.0656	0.3244		-2	-3	8.0	-0.94
c.157G>C	G53R 2D AIThe SynGAP1 missense variant G53R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of tools (5 pathogenic vs. 3 benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.1583C>T	P528L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Because the majority of evidence points to a deleterious effect and no ClinVar annotation exists to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-13.752	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.1	0.61	Ambiguous	0.96	Ambiguous	0.19	Likely Benign	0.555	Likely Pathogenic	-9.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.1975	0.5574		-3	-3	5.4	16.04
c.155C>G	S52W 2D AIThe SynGAP1 missense variant S52W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and no high‑accuracy consensus or folding‑stability evidence contradicts this trend. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.457753	Uncertain	0.499	0.677	0.000											-8.649	Likely Pathogenic	0.909	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-1.85	Neutral	0.986	Probably Damaging	0.968	Probably Damaging	4.05	Benign	0.00	Affected			0.0580	0.6254		-2	-3	-0.1	99.14
c.1565A>T	E522V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-11.985	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.09	Likely Benign	0.2	0.00	Likely Benign	0.05	Likely Benign	0.18	Likely Benign	0.751	Likely Pathogenic	-6.59	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.0537	0.4514		-2	-2	7.7	-29.98
c.1301T>G	V434G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as pathogenic. Taken together, the overwhelming majority of evidence indicates a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-12.519	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous	3.08	Destabilizing	0.0	4.37	Destabilizing	3.73	Destabilizing	1.91	Destabilizing	0.564	Likely Pathogenic	-5.16	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.07	Tolerated			0.1758	0.2408		-1	-3	-4.6	-42.08
c.1301T>C	V434A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V434A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; FoldX and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-8.531	Likely Pathogenic	0.441	Ambiguous	Likely Benign	1.72	Ambiguous	0.0	2.51	Destabilizing	2.12	Destabilizing	1.00	Destabilizing	0.238	Likely Benign	-2.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.75	Tolerated			0.2338	0.2292		0	0	-2.4	-28.05
c.1301T>A	V434D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign are SIFT and FATHMM; all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictors and the corroborating high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-14.765	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	3.26	Destabilizing	0.0	3.33	Destabilizing	3.30	Destabilizing	1.78	Destabilizing	0.592	Likely Pathogenic	-5.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.13	Tolerated			0.1307	0.0741		-2	-3	-7.7	15.96
c.1300G>T	V434F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434F is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; SGM‑Consensus predicts pathogenic; Foldetta predicts pathogenic. All predictions are available and none are inconclusive. Based on the overall distribution of predictions, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-12.553	Likely Pathogenic	0.672	Likely Pathogenic	Likely Benign	3.64	Destabilizing	0.1	3.27	Destabilizing	3.46	Destabilizing	0.27	Likely Benign	0.417	Likely Benign	-3.93	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.44	Benign	0.04	Affected			0.0596	0.3391		-1	-1	-1.4	48.04
c.1300G>C	V434L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools, Rosetta and AlphaMissense‑Default, give uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta, a protein‑folding stability method, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V434L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-8.697	Likely Pathogenic	0.477	Ambiguous	Likely Benign	-0.05	Likely Benign	0.0	1.02	Ambiguous	0.49	Likely Benign	0.20	Likely Benign	0.225	Likely Benign	-2.30	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.64	Benign	0.27	Tolerated			0.0895	0.3813		2	1	-0.4	14.03
c.1298C>G	A433G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach a consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. The protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is therefore treated as unavailable evidence. Overall, the collective predictions strongly suggest that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-5.044	Likely Benign	0.107	Likely Benign	Likely Benign	0.59	Ambiguous	0.0	1.21	Ambiguous	0.90	Ambiguous	0.70	Ambiguous	0.038	Likely Benign	-1.54	Neutral	0.035	Benign	0.014	Benign	3.38	Benign	0.15	Tolerated			0.1629	0.2919		1	0	-2.2	-14.03
c.1566A>C	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1298C>A	A433E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools (premPS and AlphaMissense‑Default) give uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports benign. No prediction is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-8.210	Likely Pathogenic	0.506	Ambiguous	Likely Benign	-0.20	Likely Benign	0.0	0.15	Likely Benign	-0.03	Likely Benign	0.58	Ambiguous	0.148	Likely Benign	-1.65	Neutral	0.998	Probably Damaging	0.824	Possibly Damaging	3.42	Benign	0.18	Tolerated			0.0783	0.1695		0	-1	-5.3	58.04
c.1297G>T	A433S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or likely benign. Only polyPhen‑2 (HumDiv) predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely benign classification; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence points to a benign impact for A433S, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-3.861	Likely Benign	0.077	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	0.41	Likely Benign	0.19	Likely Benign	-0.21	Likely Benign	0.077	Likely Benign	0.35	Neutral	0.597	Possibly Damaging	0.391	Benign	3.46	Benign	0.28	Tolerated			0.1938	0.3975		1	1	-2.6	16.00
c.1566A>T	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1567A>C	N523H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523H is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are Rosetta and Foldetta, while the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Uncertain results come from FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta as Benign. Overall, the preponderance of evidence points to a pathogenic effect for this variant, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-9.755	Likely Pathogenic	0.815	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.2	0.09	Likely Benign	0.33	Likely Benign	0.64	Ambiguous	0.694	Likely Pathogenic	-4.52	Deleterious	0.996	Probably Damaging	0.941	Probably Damaging	-1.40	Pathogenic	0.02	Affected			0.1132	0.3461		2	1	0.3	23.04
c.1303T>A	L435M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L435M missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-4.705	Likely Benign	0.534	Ambiguous	Likely Benign	0.24	Likely Benign	0.0	1.02	Ambiguous	0.63	Ambiguous	1.05	Destabilizing	0.233	Likely Benign	-1.74	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.17	Benign	0.01	Affected			0.0675	0.2753		4	2	-1.9	18.03
c.1303T>G	L435V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435V has no ClinVar assertion and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—favors pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. With the preponderance of pathogenic calls from both general and high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-7.134	In-Between	0.571	Likely Pathogenic	Likely Benign	2.97	Destabilizing	0.1	2.33	Destabilizing	2.65	Destabilizing	1.36	Destabilizing	0.217	Likely Benign	-2.80	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.23	Benign	0.06	Tolerated			0.1216	0.2628		2	1	0.4	-14.03
c.1561G>A	E521K 2D 3DClick to see structure in 3D Viewer AISynGAP1 E521K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. Overall, the majority of conventional tools lean toward a benign interpretation, while the high‑accuracy methods are split. Thus, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-9.596	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	-0.48	Likely Benign	0.2	0.14	Likely Benign	-0.17	Likely Benign	-0.10	Likely Benign	0.379	Likely Benign	-3.05	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	3.57	Benign	0.45	Tolerated			0.2895	0.6513		0	1	-0.4	-0.94
c.1561G>C	E521Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta predicts a benign stability change. Overall, the majority of evidence (9 benign vs. 4 pathogenic predictions) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-8.310	Likely Pathogenic	0.777	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.2	0.19	Likely Benign	-0.05	Likely Benign	-0.06	Likely Benign	0.262	Likely Benign	-2.15	Neutral	0.992	Probably Damaging	0.993	Probably Damaging	3.30	Benign	0.11	Tolerated			0.1580	0.6552		2	2	0.0	-0.98
c.1304T>C	L435S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity largely agree: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No predictions are missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-12.662	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	4.18	Destabilizing	0.0	4.09	Destabilizing	4.14	Destabilizing	1.83	Destabilizing	0.596	Likely Pathogenic	-5.63	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.18	Benign	0.01	Affected			0.2705	0.0505		-3	-2	-4.6	-26.08
c.1562A>C	E521A 2D 3DClick to see structure in 3D Viewer AISynGAP1 E521A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give conflicting results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No prediction or stability result is missing. Overall, the evidence is evenly split, with six benign and six pathogenic calls, and the two high‑accuracy tools disagree. Therefore, the variant’s impact remains uncertain; it is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-8.997	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.18	Likely Benign	0.1	0.40	Likely Benign	0.29	Likely Benign	0.11	Likely Benign	0.395	Likely Benign	-4.12	Deleterious	0.998	Probably Damaging	0.999	Probably Damaging	3.28	Benign	0.13	Tolerated			0.4041	0.5918		0	-1	5.3	-58.04
c.1562A>G	E521G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E521G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it is a 2‑vs‑2 split and is treated as unavailable. Overall, the majority of evidence points to a benign impact. The variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-6.636	Likely Benign	0.767	Likely Pathogenic	Likely Benign	0.18	Likely Benign	0.1	0.58	Ambiguous	0.38	Likely Benign	0.14	Likely Benign	0.289	Likely Benign	-3.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2932	0.5455		0	-2	3.1	-72.06
c.1562A>T	E521V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for E521V, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-10.297	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.49	Likely Benign	0.40	Likely Benign	0.21	Likely Benign	0.413	Likely Benign	-5.15	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.05	Affected			0.0913	0.7104		-2	-2	7.7	-29.98
c.1563G>C	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E521D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a Benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1563G>T	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521D missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. The high‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1564G>A	E522K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E522K has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, both polyPhen‑2 versions, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further indicate AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus also predicts Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts Benign. No prediction is available from FoldX (Uncertain). Overall, the majority of high‑confidence tools lean toward pathogenicity, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-12.637	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	-0.69	Ambiguous	0.1	0.14	Likely Benign	-0.28	Likely Benign	-0.13	Likely Benign	0.631	Likely Pathogenic	-3.81	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	-1.09	Pathogenic	0.23	Tolerated			0.2019	0.4291		0	1	-0.4	-0.94
c.1564G>C	E522Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E522Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools show a split: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods reinforce this pattern: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also labels it likely pathogenic, while Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a pathogenic impact. This assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.861	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	-0.13	Likely Benign	0.1	-0.06	Likely Benign	-0.10	Likely Benign	0.03	Likely Benign	0.560	Likely Pathogenic	-2.85	Deleterious	0.992	Probably Damaging	0.993	Probably Damaging	-1.33	Pathogenic	0.07	Tolerated			0.0944	0.4130		2	2	0.0	-0.98
c.1565A>C	E522A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E522A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, 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. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the preponderance of evidence (10 pathogenic vs. 4 benign predictions) indicates that E522A is most likely pathogenic, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.509	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	0.01	Likely Benign	0.10	Likely Benign	0.40	Likely Benign	0.739	Likely Pathogenic	-5.67	Deleterious	0.998	Probably Damaging	0.999	Probably Damaging	-1.34	Pathogenic	0.02	Affected			0.3137	0.4128		0	-1	5.3	-58.04
c.1565A>G	E522G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522G missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as deleterious. No tool reports a benign outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX, Rosetta, and premPS are uncertain and are treated as unavailable evidence. Overall, the computational evidence overwhelmingly points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.053	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.0	1.62	Ambiguous	1.17	Ambiguous	0.58	Ambiguous	0.823	Likely Pathogenic	-6.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.2672	0.3654		0	-2	3.1	-72.06
c.1297G>C	A433P 2D 3DClick to see structure in 3D Viewer AISynGAP1 A433P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, and FATHMM. Those that predict pathogenicity comprise FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The remaining tools, premPS and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-9.887	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	2.48	Destabilizing	0.0	7.09	Destabilizing	4.79	Destabilizing	0.55	Ambiguous	0.217	Likely Benign	-2.64	Deleterious	0.998	Probably Damaging	0.820	Possibly Damaging	3.37	Benign	0.07	Tolerated			0.1471	0.4150		1	-1	-3.4	26.04
c.1297G>A	A433T 2D AIThe SynGAP1 A433T missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-5.499	Likely Benign	0.080	Likely Benign	Likely Benign	0.35	Likely Benign	0.5	-0.02	Likely Benign	0.17	Likely Benign	0.40	Likely Benign	0.088	Likely Benign	-1.41	Neutral	0.964	Probably Damaging	0.481	Possibly Damaging	3.41	Benign	0.08	Tolerated			0.0891	0.5554		1	0	-2.5	30.03
c.1296T>G	C432W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no counter‑evidence. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-13.936	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.17	Ambiguous	0.4	0.72	Ambiguous	0.95	Ambiguous	0.58	Ambiguous	0.433	Likely Benign	-10.50	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.43	Benign	0.00	Affected			0.1217	0.3246		-8	-2	-3.4	83.07
c.1292T>A	L431Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L431Q resides in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic; this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-12.399	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	2.69	Destabilizing	0.0	2.37	Destabilizing	2.53	Destabilizing	1.99	Destabilizing	0.493	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	2.92	Benign	0.01	Affected			0.1036	0.1088		-2	-2	-7.3	14.97
c.1569C>G	N523K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include FoldX and Foldetta, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. Uncertain results are reported only by Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence supports a pathogenic classification for this variant, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-12.276	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	-0.17	Likely Benign	0.2	-0.58	Ambiguous	-0.38	Likely Benign	0.73	Ambiguous	0.607	Likely Pathogenic	-5.35	Deleterious	0.972	Probably Damaging	0.728	Possibly Damaging	-1.30	Pathogenic	0.04	Affected			0.1837	0.2866		1	0	-0.4	14.07
c.1291C>G	L431V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L431V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are FoldX, premPS, PROVEAN, and polyPhen‑2 HumDiv. Four tools (Rosetta, Foldetta, ESM1b, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 1‑to‑1 split between benign and pathogenic signals, and Foldetta also yields an uncertain outcome. Overall, the balance of evidence—including the higher number of benign predictions and the benign call from the most accurate tool—suggests that the variant is most likely benign. This conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-7.949	In-Between	0.505	Ambiguous	Likely Benign	2.17	Destabilizing	0.0	1.50	Ambiguous	1.84	Ambiguous	1.32	Destabilizing	0.093	Likely Benign	-2.58	Deleterious	0.861	Possibly Damaging	0.332	Benign	3.04	Benign	0.20	Tolerated			0.1377	0.3198		2	1	0.4	-14.03
c.1570T>C	C524R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated in‑silico tools, all pathogenic‑predicating algorithms—REVEL, SGM‑Consensus, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return a pathogenic or likely pathogenic verdict. The only tool with an inconclusive result is FoldX, which is treated as unavailable. High‑accuracy predictors reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-14.337	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	-0.53	Ambiguous	0.5	9.04	Destabilizing	4.26	Destabilizing	1.62	Destabilizing	0.917	Likely Pathogenic	-11.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.40	Pathogenic	0.00	Affected			0.2031	0.1463		-4	-3	-7.0	53.05
c.1291C>A	L431M 2D AIThe SynGAP1 missense variant L431M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain predictions come from Rosetta, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable. Overall, the balance of evidence, especially from the high‑accuracy tools, favors a benign classification. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-7.471	In-Between	0.375	Ambiguous	Likely Benign	0.18	Likely Benign	0.3	0.50	Ambiguous	0.34	Likely Benign	1.07	Destabilizing	0.102	Likely Benign	-1.50	Neutral	0.995	Probably Damaging	0.849	Possibly Damaging	2.94	Benign	0.02	Affected			0.0748	0.3121		4	2	-1.9	18.03
c.1570T>G	C524G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change at residue 524 (C524G) is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while FoldX and Foldetta are uncertain. No tool predicts a benign effect. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the evidence strongly favors a pathogenic impact for C524G, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-13.597	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.2	2.00	Destabilizing	1.54	Ambiguous	1.66	Destabilizing	0.924	Likely Pathogenic	-11.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.00	Affected			0.3579	0.2745		-3	-3	-2.9	-46.09
c.1290G>T	M430I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. Predictions that are inconclusive are FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, while Foldetta’s combined FoldX‑MD/Rosetta output is unavailable due to the uncertain FoldX result. Overall, the evidence overwhelmingly supports a benign classification for M430I, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-4.655	Likely Benign	0.420	Ambiguous	Likely Benign	1.22	Ambiguous	0.1	-0.29	Likely Benign	0.47	Likely Benign	0.65	Ambiguous	0.068	Likely Benign	-1.62	Neutral	0.134	Benign	0.025	Benign	3.54	Benign	0.40	Tolerated	3.37	29	0.1524	0.4116		1	2	2.6	-18.03
c.1290G>C	M430I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the remaining predictions (FoldX, premPS, AlphaMissense‑Default) are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also classifies the variant as benign. Taken together, the consensus of both general and high‑accuracy predictors is that M430I is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-4.655	Likely Benign	0.420	Ambiguous	Likely Benign	1.22	Ambiguous	0.1	-0.29	Likely Benign	0.47	Likely Benign	0.65	Ambiguous	0.068	Likely Benign	-1.62	Neutral	0.134	Benign	0.025	Benign	3.54	Benign	0.40	Tolerated	3.37	29	0.1524	0.4116		1	2	2.6	-18.03
c.128G>T	G43V 2D AIThe SynGAP1 missense variant G43V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431462	Uncertain	0.396	0.762	0.375											-3.745	Likely Benign	0.081	Likely Benign	Likely Benign										0.115	Likely Benign	-0.79	Neutral	0.320	Benign	0.140	Benign	4.28	Benign	0.00	Affected			0.1156	0.3120		-1	-3	4.6	42.08
c.128G>A	G43D 2D AIThe SynGAP1 missense variant G43D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431462	Uncertain	0.396	0.762	0.375											-5.867	Likely Benign	0.204	Likely Benign	Likely Benign										0.082	Likely Benign	-0.84	Neutral	0.870	Possibly Damaging	0.500	Possibly Damaging	4.21	Benign	0.00	Affected			0.2018	0.2339		1	-1	-3.1	58.04
c.1289T>G	M430R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. The remaining tools—FoldX, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of consensus tools lean toward a benign classification, while a subset of high‑accuracy methods suggest pathogenicity, leaving the variant’s impact ambiguous. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-10.636	Likely Pathogenic	0.558	Ambiguous	Likely Benign	0.98	Ambiguous	0.1	0.47	Likely Benign	0.73	Ambiguous	0.83	Ambiguous	0.153	Likely Benign	-2.87	Deleterious	0.620	Possibly Damaging	0.046	Benign	3.48	Benign	0.38	Tolerated			0.1775	0.1652		0	-1	-6.4	24.99
c.1571G>A	C524Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS is the sole tool predicting a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.032	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.20	Destabilizing	1.4	6.24	Destabilizing	4.72	Destabilizing	0.18	Likely Benign	0.863	Likely Pathogenic	-10.94	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.36	Pathogenic	0.00	Affected			0.1496	0.3911		0	-2	-3.8	60.04
c.1569C>A	N523K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include FoldX and Foldetta, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. Uncertain results are reported only by Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence supports a pathogenic classification for this variant, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-12.276	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	-0.17	Likely Benign	0.2	-0.58	Ambiguous	-0.38	Likely Benign	0.73	Ambiguous	0.607	Likely Pathogenic	-5.35	Deleterious	0.972	Probably Damaging	0.728	Possibly Damaging	-1.30	Pathogenic	0.04	Affected			0.1837	0.2866		1	0	-0.4	14.07
c.1292T>C	L431P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L431P (ClinVar ID 661045.0) is reported as Pathogenic and is not present in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: 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 the overwhelming consensus of pathogenic predictions and the ClinVar designation, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000					Likely Pathogenic		1				-14.222	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	6.78	Destabilizing	0.3	11.59	Destabilizing	9.19	Destabilizing	2.29	Destabilizing	0.659	Likely Pathogenic	-6.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.91	Benign	0.05	Affected	3.37	29	0.3484	0.2163		-3	-3	-5.4	-16.04	222.4	62.8	0.1	0.0	0.1	0.0	X							Potentially Pathogenic	The iso-butyl side chain of Leu431, located in an α helix (res. Met414-Glu436), packs against other hydrophobic residues in an interhelix space (e.g., Val434, Leu435, Leu696, Leu711) in the WT simulations. While the backbone amide group of Leu431 forms an H-bond with the carbonyl group of His427, the cyclic five-membered pyrrolidine ring of Pro431, lacking the necessary amide group, cannot do the same. Thus, although the cyclic five-membered pyrrolidine ring of Pro431 packs almost as favorably as the side chain of Leu431 in the hydrophobic niche, the residue swap causes the α helix to partially unfold in the variant simulations.
c.1567A>G	N523D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 N523D missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the predictions are mixed, but the majority of high‑confidence tools lean toward pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-8.955	Likely Pathogenic	0.641	Likely Pathogenic	Likely Benign	0.14	Likely Benign	0.2	1.10	Ambiguous	0.62	Ambiguous	0.56	Ambiguous	0.272	Likely Benign	-3.57	Deleterious	0.112	Benign	0.079	Benign	-1.25	Pathogenic	0.22	Tolerated			0.1553	0.1866		2	1	0.0	0.98
c.1567A>T	N523Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. With eight tools supporting pathogenicity versus three supporting benign, the overall evidence points to a likely pathogenic impact. This conclusion is consistent with the absence of a ClinVar classification, as no contradictory status exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-11.701	Likely Pathogenic	0.836	Likely Pathogenic	Ambiguous	0.13	Likely Benign	0.3	-1.36	Ambiguous	-0.62	Ambiguous	-0.01	Likely Benign	0.624	Likely Pathogenic	-7.34	Deleterious	0.999	Probably Damaging	0.972	Probably Damaging	-1.39	Pathogenic	0.10	Tolerated			0.0586	0.3388		-2	-2	2.2	49.07
c.1295G>T	C432F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432F is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-12.862	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	-0.44	Likely Benign	0.2	-0.34	Likely Benign	-0.39	Likely Benign	0.57	Ambiguous	0.434	Likely Benign	-10.50	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.01	Affected			0.1090	0.3956		-4	-2	0.3	44.04
c.1568A>C	N523T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The premPS score is uncertain and does not contribute to the consensus. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding result is missing or inconclusive. Overall, the majority of tools (10/14) predict pathogenicity, whereas four predict benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-10.056	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.47	Likely Benign	0.2	-0.22	Likely Benign	0.13	Likely Benign	0.65	Ambiguous	0.646	Likely Pathogenic	-5.33	Deleterious	0.898	Possibly Damaging	0.592	Possibly Damaging	-1.40	Pathogenic	0.02	Affected			0.0920	0.3780		0	0	2.8	-13.00
c.1295G>C	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.417	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1295G>A	C432Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C432Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while benign predictions are reported by REVEL, Rosetta, FATHMM, and Foldetta. Tools with uncertain or missing results (FoldX, premPS) are not considered evidence. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predict pathogenicity, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of predictions support a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-13.720	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.62	Ambiguous	0.3	0.31	Likely Benign	0.47	Likely Benign	0.71	Ambiguous	0.441	Likely Benign	-10.50	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.02	Affected			0.0857	0.3438		0	-2	-3.8	60.04
c.1568A>G	N523S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and FATHMM. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) returned uncertain or inconclusive results. For high‑accuracy assessment, AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports an uncertain folding‑stability change. Taken together, the majority of evidence (five benign versus three pathogenic predictions) points to a benign effect, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-6.188	Likely Benign	0.552	Ambiguous	Likely Benign	0.64	Ambiguous	0.2	0.66	Ambiguous	0.65	Ambiguous	0.17	Likely Benign	0.492	Likely Benign	-4.31	Deleterious	0.976	Probably Damaging	0.410	Benign	-1.27	Pathogenic	0.27	Tolerated			0.2213	0.4178		1	1	2.7	-27.03
c.1294T>G	C432G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-10.247	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.0	2.25	Destabilizing	1.81	Ambiguous	1.60	Destabilizing	0.631	Likely Pathogenic	-11.46	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.2796	0.2130		-3	-3	-2.9	-46.09
c.1294T>C	C432R 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 missense variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. The majority of algorithms predict a pathogenic impact: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta report uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains inconclusive. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-13.858	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.03	Ambiguous	0.2	2.05	Destabilizing	1.54	Ambiguous	1.73	Destabilizing	0.690	Likely Pathogenic	-11.46	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.01	Affected			0.1359	0.1766		-4	-3	-7.0	53.05
c.1294T>A	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.496	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1568A>T	N523I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N523I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools report uncertain results: Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while 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 outputs, remains inconclusive. Overall, the preponderance of evidence (eight pathogenic versus three benign predictions) suggests that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-12.862	Likely Pathogenic	0.761	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	-1.53	Ambiguous	-0.64	Ambiguous	0.33	Likely Benign	0.726	Likely Pathogenic	-8.18	Deleterious	0.989	Probably Damaging	0.946	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.0627	0.3714		-2	-3	8.0	-0.94
c.1292T>G	L431R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L431R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-14.777	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.45	Destabilizing	0.0	4.76	Destabilizing	4.11	Destabilizing	1.93	Destabilizing	0.654	Likely Pathogenic	-5.47	Deleterious	0.997	Probably Damaging	0.833	Possibly Damaging	2.93	Benign	0.00	Affected			0.1191	0.0730		-3	-2	-8.3	43.03
c.1289T>A	M430K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and ESM1b. The remaining tools—FoldX, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors a pathogenic outcome; Foldetta remains uncertain. Overall, the majority of individual predictors lean toward a benign interpretation, whereas the SGM Consensus suggests pathogenicity. Given the lack of ClinVar evidence, there is no contradiction with existing clinical annotations. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-10.816	Likely Pathogenic	0.494	Ambiguous	Likely Benign	0.78	Ambiguous	0.1	0.44	Likely Benign	0.61	Ambiguous	0.86	Ambiguous	0.149	Likely Benign	-2.66	Deleterious	0.134	Benign	0.033	Benign	3.47	Benign	0.32	Tolerated			0.1660	0.1271		0	-1	-5.8	-3.02
c.2405G>C	G802A 2D AIThe SynGAP1 missense variant G802A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that G802A is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625											-3.584	Likely Benign	0.105	Likely Benign	Likely Benign										0.039	Likely Benign	-0.57	Neutral	0.059	Benign	0.089	Benign	2.74	Benign	0.02	Affected			0.3779	0.4554		1	0	2.2	14.03
c.1063G>C	G355R 2D AIThe SynGAP1 missense variant G355R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evaluated tools predict a pathogenic impact, whereas a minority predict benign. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-11.022	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.61	Ambiguous	1.4	0.10	Likely Benign	0.36	Likely Benign	0.60	Ambiguous	0.340	Likely Benign	-6.74	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.1041	0.4567		-3	-2	-4.1	99.14
c.1063G>A	G355R 2D AIThe SynGAP1 missense variant G355R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evaluated tools predict a pathogenic impact, whereas a minority predict benign. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-11.022	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.61	Ambiguous	1.4	0.10	Likely Benign	0.36	Likely Benign	0.60	Ambiguous	0.340	Likely Benign	-6.74	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.1041	0.4567		-3	-2	-4.1	99.14
c.2411A>T	D804V 2D AIThe SynGAP1 missense variant D804V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. The AlphaMissense‑Optimized score is uncertain, providing no definitive evidence. High‑accuracy assessments show that the SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; AlphaMissense‑Optimized remains inconclusive, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for D804V, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-8.143	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous										0.402	Likely Benign	-4.77	Deleterious	0.997	Probably Damaging	0.951	Probably Damaging	1.19	Pathogenic	0.01	Affected			0.1196	0.6981		-2	-3	7.7	-15.96
c.2412C>A	D804E 2D AIThe SynGAP1 D804E missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign” (3 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote) as benign, and Foldetta results are unavailable. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-4.155	Likely Benign	0.243	Likely Benign	Likely Benign										0.035	Likely Benign	-2.03	Neutral	0.400	Benign	0.138	Benign	1.26	Pathogenic	0.04	Affected			0.1765	0.6850		3	2	0.0	14.03
c.2412C>G	D804E 2D AIThe SynGAP1 D804E missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign” (3 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote) as benign, and Foldetta results are unavailable. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-4.155	Likely Benign	0.243	Likely Benign	Likely Benign										0.038	Likely Benign	-2.03	Neutral	0.400	Benign	0.138	Benign	1.26	Pathogenic	0.04	Affected			0.1765	0.6850		3	2	0.0	14.03
c.2413C>A	L805M 2D AIThe SynGAP1 missense variant L805M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and no Foldetta stability data are available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-4.229	Likely Benign	0.133	Likely Benign	Likely Benign										0.034	Likely Benign	-0.67	Neutral	0.029	Benign	0.033	Benign	2.39	Pathogenic	0.00	Affected			0.0911	0.3867		4	2	-1.9	18.03
c.1061C>G	A354G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A354G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. Predictions marked uncertain (Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a benign impact for A354G, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-4.285	Likely Benign	0.113	Likely Benign	Likely Benign	0.41	Likely Benign	0.0	1.24	Ambiguous	0.83	Ambiguous	0.65	Ambiguous	0.037	Likely Benign	-1.87	Neutral	0.146	Benign	0.038	Benign	1.75	Pathogenic	0.05	Affected			0.2563	0.4777		1	0	-2.2	-14.03
c.1061C>A	A354D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A354D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Those that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, and Rosetta) return uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors a pathogenic interpretation. Foldetta’s stability prediction is uncertain. Overall, the majority of consensus tools lean toward a benign effect, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-7.914	In-Between	0.725	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	1.10	Ambiguous	0.66	Ambiguous	0.57	Ambiguous	0.087	Likely Benign	-1.49	Neutral	0.255	Benign	0.053	Benign	1.75	Pathogenic	0.07	Tolerated			0.1759	0.1345		0	-2	-5.3	44.01
c.2413C>G	L805V 2D AIThe SynGAP1 missense variant L805V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-2.445	Likely Benign	0.094	Likely Benign	Likely Benign										0.027	Likely Benign	-1.16	Neutral	0.003	Benign	0.008	Benign	2.65	Benign	0.00	Affected			0.1553	0.3493		2	1	0.4	-14.03
c.2414T>A	L805Q 2D AIThe SynGAP1 missense variant L805Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. three benign predictions, with a pathogenic SGM Consensus) indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-6.244	Likely Benign	0.427	Ambiguous	Likely Benign										0.152	Likely Benign	-2.66	Deleterious	0.927	Possibly Damaging	0.690	Possibly Damaging	2.37	Pathogenic	0.00	Affected			0.1215	0.1265		-2	-2	-7.3	14.97
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	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625					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	0.3128	0.1650		-3	-3	-5.4	-16.04
c.1060G>T	A354S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A354S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. Taken together, the overwhelming majority of evidence indicates that A354S is most likely benign, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-3.005	Likely Benign	0.081	Likely Benign	Likely Benign	0.02	Likely Benign	0.1	0.27	Likely Benign	0.15	Likely Benign	-0.10	Likely Benign	0.071	Likely Benign	0.28	Neutral	0.005	Benign	0.001	Benign	1.76	Pathogenic	0.21	Tolerated			0.2829	0.5117		1	1	-2.6	16.00
c.1063G>T	G355W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G355W is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and premPS, and pathogenic predictions from SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-12.316	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.5	0.88	Ambiguous	1.02	Ambiguous	0.18	Likely Benign	0.455	Likely Benign	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.0796	0.4360		-7	-2	-0.5	129.16
c.2410G>T	D804Y 2D AIThe SynGAP1 missense variant D804Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-8.356	Likely Pathogenic	0.782	Likely Pathogenic	Likely Benign										0.357	Likely Benign	-5.16	Deleterious	0.999	Probably Damaging	0.983	Probably Damaging	1.18	Pathogenic	0.01	Affected			0.0886	0.6653		-4	-3	2.2	48.09
c.2405G>T	G802V 2D AIThe SynGAP1 missense variant G802V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign. No Foldetta stability analysis is available for this variant. Overall, the consensus of the available predictions indicates that G802V is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625											-3.871	Likely Benign	0.126	Likely Benign	Likely Benign										0.078	Likely Benign	-1.49	Neutral	0.411	Benign	0.321	Benign	2.67	Benign	0.00	Affected			0.1345	0.3533		-1	-3	4.6	42.08
c.2407A>C	K803Q 2D AIThe SynGAP1 missense variant K803Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-2.792	Likely Benign	0.305	Likely Benign	Likely Benign										0.108	Likely Benign	-2.01	Neutral	0.984	Probably Damaging	0.773	Possibly Damaging	2.36	Pathogenic	0.00	Affected			0.4810	0.1398		1	1	0.4	-0.04
c.2407A>G	K803E 2D AIThe SynGAP1 missense variant K803E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign) and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-3.889	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.172	Likely Benign	-2.06	Neutral	0.896	Possibly Damaging	0.596	Possibly Damaging	2.38	Pathogenic	0.00	Affected			0.4043	0.1357		0	1	0.4	0.94
c.2408A>C	K803T 2D AIThe SynGAP1 missense variant K803T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicate it is likely pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus indicates it is likely pathogenic; a Foldetta stability analysis is not available. Overall, the balance of evidence points to a pathogenic effect for K803T, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-3.571	Likely Benign	0.584	Likely Pathogenic	Likely Benign										0.121	Likely Benign	-2.90	Deleterious	0.946	Possibly Damaging	0.741	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.2417	0.4395		0	-1	3.2	-27.07
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	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625					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	0.4857	0.1715		3	2	-0.6	28.01
c.2408A>T	K803I 2D AIThe SynGAP1 K803I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for K803I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.207	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.06	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1425	0.3889		-2	-3	8.4	-15.01
c.2409A>C	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools predict pathogenicity (five) than benignity (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.2409A>T	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.240A>C	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.240A>T	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.2410G>A	D804N 2D AIThe SynGAP1 D804N variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools predict a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Thus, based on the current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-4.681	Likely Benign	0.522	Ambiguous	Likely Benign										0.104	Likely Benign	-2.62	Deleterious	0.400	Benign	0.212	Benign	1.22	Pathogenic	0.06	Tolerated			0.1528	0.7393		2	1	0.0	-0.98
c.2410G>C	D804H 2D AIThe SynGAP1 D804H missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that D804H is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-5.100	Likely Benign	0.821	Likely Pathogenic	Ambiguous										0.296	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	1.19	Pathogenic	0.01	Affected			0.1859	0.7607		1	-1	0.3	22.05
c.1060G>C	A354P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A354P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, SIFT, and FATHMM, while Rosetta and premPS are inconclusive. The high‑accuracy consensus from AlphaMissense‑Optimized and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) both indicate a benign outcome, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Overall, the majority of evidence points to a benign effect for A354P, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-5.971	Likely Benign	0.239	Likely Benign	Likely Benign	2.66	Destabilizing	0.2	1.55	Ambiguous	2.11	Destabilizing	0.57	Ambiguous	0.241	Likely Benign	-1.66	Neutral	0.001	Benign	0.002	Benign	1.76	Pathogenic	0.04	Affected			0.2259	0.5884		1	-1	-3.4	26.04
c.2414T>G	L805R 2D AIThe SynGAP1 missense variant L805R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence from the broader set of predictors leans toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-6.640	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.196	Likely Benign	-3.00	Deleterious	0.927	Possibly Damaging	0.617	Possibly Damaging	2.37	Pathogenic	0.00	Affected			0.1372	0.0908		-3	-2	-8.3	43.03
c.2416T>A	F806I 2D AIThe SynGAP1 missense variant F806I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the balance of evidence from the consensus of prediction algorithms points to a pathogenic impact for F806I. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-5.040	Likely Benign	0.744	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-3.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.15	Pathogenic	0.03	Affected			0.2583	0.1357		1	0	1.7	-34.02
c.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	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500					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	0.2485	0.2500		7	3	4.1	-16.00
c.1058T>A	L353Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L353Q missense variant has no ClinVar entry and is absent from gnomAD. Among in‑silico predictors, only REVEL classifies it as benign, whereas the majority—FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—label it pathogenic. Predictions marked uncertain include Rosetta, Foldetta, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of pathogenic predictions outweighs the single benign call, and no ClinVar record contradicts this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-7.074	In-Between	0.884	Likely Pathogenic	Ambiguous	2.38	Destabilizing	0.2	1.41	Ambiguous	1.90	Ambiguous	2.00	Destabilizing	0.388	Likely Benign	-3.56	Deleterious	0.947	Possibly Damaging	0.556	Possibly Damaging	1.30	Pathogenic	0.01	Affected			0.1098	0.1303		-2	-2	-7.3	14.97
c.2422G>A	V808I 2D AIThe SynGAP1 missense variant V808I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign and the SGM‑Consensus (majority vote) is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-4.190	Likely Benign	0.151	Likely Benign	Likely Benign										0.051	Likely Benign	-0.67	Neutral	0.659	Possibly Damaging	0.191	Benign	2.33	Pathogenic	0.00	Affected			0.0935	0.4282		4	3	0.3	14.03
c.2422G>C	V808L 2D AIThe SynGAP1 missense variant V808L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for V808L, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-4.723	Likely Benign	0.306	Likely Benign	Likely Benign										0.188	Likely Benign	-1.82	Neutral	0.911	Possibly Damaging	0.621	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1166	0.4745		2	1	-0.4	14.03
c.2422G>T	V808L 2D AIThe SynGAP1 missense variant V808L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-4.723	Likely Benign	0.306	Likely Benign	Likely Benign										0.188	Likely Benign	-1.82	Neutral	0.911	Possibly Damaging	0.621	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1166	0.4745		2	1	-0.4	14.03
c.1057C>G	L353V 2D AISynGAP1 missense variant L353V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools predicting pathogenicity are FoldX and FATHMM, while Rosetta gives an uncertain result. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the balance of evidence favors a benign effect; this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-2.100	Likely Benign	0.078	Likely Benign	Likely Benign	3.08	Destabilizing	0.9	1.48	Ambiguous	2.28	Destabilizing	-0.45	Likely Benign	0.074	Likely Benign	1.54	Neutral	0.002	Benign	0.002	Benign	1.46	Pathogenic	0.89	Tolerated			0.1567	0.3829		2	1	0.4	-14.03
c.2423T>A	V808E 2D AIThe SynGAP1 missense variant V808E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic, and Foldetta data are not available. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-9.078	Likely Pathogenic	0.888	Likely Pathogenic	Ambiguous										0.307	Likely Benign	-2.84	Deleterious	0.999	Probably Damaging	0.958	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1129	0.2787		-2	-2	-7.7	29.98
c.1057C>A	L353M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353M has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-6.943	Likely Benign	0.206	Likely Benign	Likely Benign	0.10	Likely Benign	0.0	1.28	Ambiguous	0.69	Ambiguous	0.60	Ambiguous	0.117	Likely Benign	-0.47	Neutral	0.744	Possibly Damaging	0.289	Benign	1.33	Pathogenic	0.03	Affected			0.0847	0.4080		4	2	-1.9	18.03
c.2423T>C	V808A 2D AIThe SynGAP1 missense variant V808A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign verdict, while Foldetta results are unavailable. Taken together, the majority of evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-5.091	Likely Benign	0.541	Ambiguous	Likely Benign										0.177	Likely Benign	-1.96	Neutral	0.953	Possibly Damaging	0.621	Possibly Damaging	2.31	Pathogenic	0.00	Affected			0.2748	0.2809		0	0	-2.4	-28.05
c.1055C>T	T352I 2D AISynGAP1 T352I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. With seven benign versus five pathogenic predictions and two high‑accuracy benign versus one pathogenic, the evidence leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-8.023	Likely Pathogenic	0.321	Likely Benign	Likely Benign	-0.54	Ambiguous	0.7	0.43	Likely Benign	-0.06	Likely Benign	0.09	Likely Benign	0.099	Likely Benign	-3.02	Deleterious	0.627	Possibly Damaging	0.196	Benign	1.67	Pathogenic	0.14	Tolerated			0.1009	0.6484		0	-1	5.2	12.05
c.2423T>G	V808G 2D AIThe SynGAP1 V808G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of individual predictors (five benign vs. three pathogenic) support a benign classification, and this is not contradicted by any ClinVar annotation. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-6.635	Likely Benign	0.460	Ambiguous	Likely Benign										0.268	Likely Benign	-2.94	Deleterious	0.069	Benign	0.135	Benign	2.27	Pathogenic	0.00	Affected			0.1925	0.3336		-1	-3	-4.6	-42.08
c.2425A>C	S809R 2D AIThe SynGAP1 missense variant S809R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into three groups: benign predictions from REVEL, PROVEAN, and FATHMM; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; and uncertain predictions from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign. Protein‑folding stability analysis with Foldetta is unavailable. Overall, the balance of evidence, particularly the benign consensus from high‑accuracy tools, suggests the variant is most likely benign, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-7.062	In-Between	0.935	Likely Pathogenic	Ambiguous										0.085	Likely Benign	-1.50	Neutral	0.784	Possibly Damaging	0.472	Possibly Damaging	2.51	Benign	0.01	Affected			0.0954	0.3702		0	-1	-3.7	69.11
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	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000					Uncertain		1				-7.913	In-Between	0.936	Likely Pathogenic	Ambiguous	4.63	Destabilizing	0.1	10.19	Destabilizing	7.41	Destabilizing	2.17	Destabilizing	0.464	Likely Benign	-3.70	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.29	Pathogenic	0.02	Affected	3.37	25	0.3582	0.1645		-3	-3	-5.4	-16.04
c.2420A>C	Y807S 2D AIThe SynGAP1 Y807S variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on benign impact include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, while those that predict pathogenicity are PROVEAN, SIFT, and FATHMM. AlphaMissense‑Default is uncertain, whereas AlphaMissense‑Optimized predicts benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans toward pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools (four benign vs. three pathogenic) suggest a benign effect, and the high‑accuracy AlphaMissense‑Optimized also predicts benign, while the SGM Consensus predicts pathogenic. Based on the balance of evidence, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-5.517	Likely Benign	0.384	Ambiguous	Likely Benign										0.093	Likely Benign	-3.90	Deleterious	0.136	Benign	0.067	Benign	2.44	Pathogenic	0.01	Affected			0.4561	0.1884		-3	-2	0.5	-76.10
c.2416T>C	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2416T>G	F806V 2D AIThe SynGAP1 missense variant F806V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; a Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of prediction algorithms points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-4.548	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-3.79	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.16	Pathogenic	0.02	Affected			0.2464	0.1325		-1	-1	1.4	-48.04
c.2417T>A	F806Y 2D AIThe SynGAP1 missense variant F806Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also classifies it as benign, and Foldetta results are unavailable. Taken together, the majority of evidence points to a benign effect, and this conclusion does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-5.229	Likely Benign	0.404	Ambiguous	Likely Benign										0.162	Likely Benign	-1.51	Neutral	0.997	Probably Damaging	0.987	Probably Damaging	2.32	Pathogenic	0.03	Affected			0.1746	0.1437		7	3	-4.1	16.00
c.1060G>A	A354T 2D AIThe SynGAP1 missense variant A354T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic effect. High‑accuracy assessments further support a benign outcome: 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 stability calculations, also reports a benign result. No predictions or folding‑stability analyses are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.381329	Uncertain	0.882	0.335	0.125											-2.812	Likely Benign	0.070	Likely Benign	Likely Benign	0.37	Likely Benign	0.7	0.11	Likely Benign	0.24	Likely Benign	-0.52	Ambiguous	0.097	Likely Benign	1.72	Neutral	0.002	Benign	0.001	Benign	1.75	Pathogenic	0.45	Tolerated			0.1731	0.6496		1	0	-2.5	30.03
c.2417T>G	F806C 2D AIThe SynGAP1 missense variant F806C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while SGM‑Consensus remains likely pathogenic; Foldetta results are unavailable. Based on the predominance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-8.565	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous										0.266	Likely Benign	-4.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.3071	0.1125		-4	-2	-0.3	-44.04
c.2418C>A	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2418C>G	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, SIFT, and ESM1b, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict (3/4 pathogenic votes). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta stability assessment is available. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion aligns with the SGM‑Consensus prediction; it does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.1058T>G	L353R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353R is not reported in ClinVar and is absent from gnomAD. In silico predictors largely agree on a deleterious effect: benign predictions are limited to REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all classify the variant as pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction contradicts the ClinVar status, which is currently unreported. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-11.213	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	3.60	Destabilizing	0.5	2.48	Destabilizing	3.04	Destabilizing	1.91	Destabilizing	0.444	Likely Benign	-4.15	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.33	Pathogenic	0.01	Affected			0.1304	0.1145		-3	-2	-8.3	43.03
c.2419T>A	Y807N 2D AIThe SynGAP1 missense variant Y807N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which is labeled Likely Pathogenic. ESM1b is uncertain. High‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, a protein‑folding stability approach that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-7.795	In-Between	0.591	Likely Pathogenic	Likely Benign										0.154	Likely Benign	-4.01	Deleterious	0.934	Possibly Damaging	0.773	Possibly Damaging	2.43	Pathogenic	0.00	Affected			0.2274	0.0704		-2	-2	-2.2	-49.07
c.2419T>C	Y807H 2D AIThe SynGAP1 missense variant Y807H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as pathogenic. AlphaMissense‑Optimized remains benign, while Foldetta results are unavailable. Overall, the majority of high‑accuracy and consensus predictors (five out of six) suggest a pathogenic impact, whereas only three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-5.879	Likely Benign	0.413	Ambiguous	Likely Benign										0.152	Likely Benign	-2.74	Deleterious	0.989	Probably Damaging	0.913	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.2530	0.0704		0	2	-1.9	-26.03
c.2419T>G	Y807D 2D AIThe SynGAP1 missense variant Y807D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for Y807D, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-7.598	In-Between	0.862	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-4.40	Deleterious	0.966	Probably Damaging	0.773	Possibly Damaging	2.42	Pathogenic	0.00	Affected			0.3944	0.0704		-4	-3	-2.2	-48.09
c.241C>G	L81V 2D AIThe SynGAP1 missense variant L81V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for L81V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-5.207	Likely Benign	0.289	Likely Benign	Likely Benign										0.038	Likely Benign	-0.51	Neutral	0.178	Benign	0.014	Benign	4.04	Benign	0.00	Affected			0.1423	0.2653		2	1	0.4	-14.03
c.2425A>G	S809G 2D AIThe SynGAP1 missense variant S809G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that S809G is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-6.100	Likely Benign	0.142	Likely Benign	Likely Benign										0.085	Likely Benign	-1.80	Neutral	0.270	Benign	0.136	Benign	2.61	Benign	0.02	Affected			0.2743	0.5369		1	0	0.4	-30.03
c.2380C>G	P794A 2D AIThe SynGAP1 missense variant P794A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875											-3.766	Likely Benign	0.056	Likely Benign	Likely Benign										0.038	Likely Benign	-0.63	Neutral	0.124	Benign	0.089	Benign	4.27	Benign	0.09	Tolerated			0.3692	0.5209		1	-1	3.4	-26.04
c.2387C>G	P796R 2D AIThe SynGAP1 P796R missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as “Likely Benign.” Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-7.053	In-Between	0.191	Likely Benign	Likely Benign										0.063	Likely Benign	-0.57	Neutral	0.002	Benign	0.002	Benign	4.28	Benign	0.01	Affected			0.1558	0.2934		0	-2	-2.9	59.07
c.2387C>T	P796L 2D AIThe SynGAP1 P796L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-5.442	Likely Benign	0.069	Likely Benign	Likely Benign										0.063	Likely Benign	-1.06	Neutral	0.325	Benign	0.182	Benign	4.24	Benign	0.01	Affected			0.2328	0.5712		-3	-3	5.4	16.04
c.2389C>A	P797T 2D AIThe SynGAP1 missense variant P797T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-6.554	Likely Benign	0.064	Likely Benign	Likely Benign										0.030	Likely Benign	-0.15	Neutral	0.901	Possibly Damaging	0.708	Possibly Damaging	4.23	Benign	0.24	Tolerated			0.1733	0.5830		0	-1	0.9	3.99
c.2389C>G	P797A 2D AIThe SynGAP1 missense variant P797A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence indicates that P797A is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-5.548	Likely Benign	0.050	Likely Benign	Likely Benign										0.037	Likely Benign	-0.33	Neutral	0.649	Possibly Damaging	0.535	Possibly Damaging	4.25	Benign	0.54	Tolerated			0.3704	0.4832		1	-1	3.4	-26.04
c.2389C>T	P797S 2D AIThe SynGAP1 missense variant P797S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for P797S, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-6.232	Likely Benign	0.068	Likely Benign	Likely Benign										0.029	Likely Benign	-0.14	Neutral	0.901	Possibly Damaging	0.637	Possibly Damaging	4.25	Benign	0.38	Tolerated			0.3634	0.5228		1	-1	0.8	-10.04
c.238A>C	K80Q 2D AIThe SynGAP1 missense variant K80Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-4.475	Likely Benign	0.662	Likely Pathogenic	Likely Benign										0.064	Likely Benign	-0.81	Neutral	0.414	Benign	0.040	Benign	3.93	Benign	0.00	Affected			0.4373	0.1132		1	1	0.4	-0.04
c.238A>G	K80E 2D AIThe SynGAP1 K80E missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Overall, the balance of evidence favors a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K80E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.605	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.034	Likely Benign	-0.91	Neutral	0.225	Benign	0.027	Benign	3.92	Benign	0.00	Affected			0.3850	0.0952		0	1	0.4	0.94
c.2390C>A	P797Q 2D AIThe SynGAP1 missense variant P797Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-6.201	Likely Benign	0.081	Likely Benign	Likely Benign										0.066	Likely Benign	-0.04	Neutral	0.940	Possibly Damaging	0.801	Possibly Damaging	4.23	Benign	0.15	Tolerated			0.1636	0.4787		0	-1	-1.9	31.01
c.2390C>G	P797R 2D AIThe SynGAP1 missense variant P797R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports “Likely Benign.” No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign outcome; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-5.642	Likely Benign	0.179	Likely Benign	Likely Benign										0.045	Likely Benign	0.00	Neutral	0.006	Benign	0.026	Benign	4.28	Benign	0.20	Tolerated			0.1549	0.3085		0	-2	-2.9	59.07
c.2390C>T	P797L 2D AIThe SynGAP1 missense variant P797L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-5.631	Likely Benign	0.072	Likely Benign	Likely Benign										0.033	Likely Benign	-0.66	Neutral	0.818	Possibly Damaging	0.637	Possibly Damaging	4.23	Benign	0.40	Tolerated			0.2550	0.6538		-3	-3	5.4	16.04
c.2392C>A	P798T 2D AIThe SynGAP1 missense variant P798T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect for P798T, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.926	Likely Benign	0.062	Likely Benign	Likely Benign										0.039	Likely Benign	-0.38	Neutral	0.901	Possibly Damaging	0.534	Possibly Damaging	4.24	Benign	0.00	Affected			0.1293	0.4854		0	-1	0.9	3.99
c.1067G>C	R356P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R356P missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FoldX, whereas a majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive are AlphaMissense‑Optimized, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, 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 R356P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-12.956	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous	0.48	Likely Benign	0.1	0.72	Ambiguous	0.60	Ambiguous	1.05	Destabilizing	0.451	Likely Benign	-6.23	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.72	Pathogenic	0.02	Affected			0.2213	0.5033		0	-2	2.9	-59.07
c.2387C>A	P796Q 2D AIThe SynGAP1 missense variant P796Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while the only tool predicting a deleterious outcome is SIFT, which labels it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign; no Foldetta stability data are available. Overall, the consensus of the majority of predictors and the high‑accuracy tools points to a benign effect for P796Q, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar classification, as no pathogenic claim is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-6.575	Likely Benign	0.084	Likely Benign	Likely Benign										0.074	Likely Benign	-0.15	Neutral	0.325	Benign	0.103	Benign	4.27	Benign	0.01	Affected			0.1562	0.4117		0	-1	-1.9	31.01
c.2386C>T	P796S 2D AIThe SynGAP1 missense variant P796S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign. Foldetta results are not available for this variant. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-5.382	Likely Benign	0.067	Likely Benign	Likely Benign										0.055	Likely Benign	0.05	Neutral	0.174	Benign	0.091	Benign	4.28	Benign	0.48	Tolerated			0.3560	0.4171		1	-1	0.8	-10.04
c.2380C>T	P794S 2D AIThe SynGAP1 missense variant P794S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875											-5.086	Likely Benign	0.079	Likely Benign	Likely Benign										0.041	Likely Benign	-0.21	Neutral	0.025	Benign	0.010	Benign	4.29	Benign	0.13	Tolerated			0.3666	0.5604		1	-1	0.8	-10.04
c.2381C>A	P794Q 2D AIThe SynGAP1 missense variant P794Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P794Q, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875											-4.641	Likely Benign	0.101	Likely Benign	Likely Benign										0.058	Likely Benign	-0.31	Neutral	0.918	Possibly Damaging	0.601	Possibly Damaging	4.24	Benign	0.02	Affected			0.1581	0.4971		0	-1	-1.9	31.01
c.2381C>G	P794R 2D AIThe SynGAP1 missense variant P794R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect for P794R, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875											-5.136	Likely Benign	0.260	Likely Benign	Likely Benign										0.083	Likely Benign	-0.73	Neutral	0.918	Possibly Damaging	0.522	Possibly Damaging	4.25	Benign	0.02	Affected			0.1467	0.3662		0	-2	-2.9	59.07
c.106C>A	H36N 2D AIThe SynGAP1 missense variant H36N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-3.614	Likely Benign	0.085	Likely Benign	Likely Benign										0.027	Likely Benign	-0.83	Neutral	0.019	Benign	0.021	Benign	4.21	Benign	0.00	Affected			0.2353	0.4258		2	1	-0.3	-23.04
c.2383C>A	P795T 2D AIThe SynGAP1 missense variant P795T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, and the only uncertain result comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-7.030	In-Between	0.060	Likely Benign	Likely Benign										0.068	Likely Benign	-0.63	Neutral	0.036	Benign	0.026	Benign	4.26	Benign	0.09	Tolerated			0.1713	0.6381		0	-1	0.9	3.99
c.2383C>G	P795A 2D AIThe SynGAP1 missense variant P795A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) 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 evidence strongly suggests that P795A is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-5.348	Likely Benign	0.049	Likely Benign	Likely Benign										0.053	Likely Benign	-0.52	Neutral	0.016	Benign	0.011	Benign	4.32	Benign	0.16	Tolerated			0.3672	0.5371		1	-1	3.4	-26.04
c.1069C>G	H357D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta also predicts a benign outcome. No prediction or folding‑stability result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-12.013	Likely Pathogenic	0.559	Ambiguous	Likely Benign	-0.23	Likely Benign	0.4	-0.27	Likely Benign	-0.25	Likely Benign	0.48	Likely Benign	0.208	Likely Benign	-1.90	Neutral	0.495	Possibly Damaging	0.169	Benign	4.22	Benign	0.08	Tolerated			0.2782	0.1976		1	-1	-0.3	-22.05
c.2384C>A	P795H 2D AIThe SynGAP1 missense variant P795H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic outcome. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-7.717	In-Between	0.121	Likely Benign	Likely Benign										0.069	Likely Benign	-0.61	Neutral	0.898	Possibly Damaging	0.477	Possibly Damaging	4.24	Benign	0.05	Affected			0.1947	0.5184		0	-2	-1.6	40.02
c.2384C>G	P795R 2D AIThe SynGAP1 missense variant P795R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT classifies the change as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that P795R is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-6.536	Likely Benign	0.221	Likely Benign	Likely Benign										0.059	Likely Benign	-1.02	Neutral	0.290	Benign	0.114	Benign	4.25	Benign	0.05	Affected			0.1430	0.4065		0	-2	-2.9	59.07
c.2384C>T	P795L 2D AIThe SynGAP1 missense variant P795L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that P795L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-2.677	Likely Benign	0.070	Likely Benign	Likely Benign										0.047	Likely Benign	-0.45	Neutral	0.016	Benign	0.010	Benign	4.27	Benign	0.04	Affected			0.2372	0.6499		-3	-3	5.4	16.04
c.1069C>A	H357N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the overwhelming majority of evidence points to a benign impact. There is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.617	In-Between	0.103	Likely Benign	Likely Benign	0.14	Likely Benign	0.2	0.31	Likely Benign	0.23	Likely Benign	0.31	Likely Benign	0.126	Likely Benign	-1.47	Neutral	0.495	Possibly Damaging	0.169	Benign	4.25	Benign	0.15	Tolerated			0.2052	0.3266		2	1	-0.3	-23.04
c.2386C>A	P796T 2D AIThe SynGAP1 P796T missense variant is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-5.399	Likely Benign	0.062	Likely Benign	Likely Benign										0.082	Likely Benign	-0.01	Neutral	0.494	Possibly Damaging	0.236	Benign	4.26	Benign	0.04	Affected			0.1705	0.4961		0	-1	0.9	3.99
c.2392C>G	P798A 2D AIThe SynGAP1 missense variant P798A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas only polyPhen‑2 HumDiv and SIFT predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus also indicates benign. Foldetta results are not available, so they do not influence the assessment. Overall, the consensus of available predictions indicates that P798A is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-4.841	Likely Benign	0.050	Likely Benign	Likely Benign										0.045	Likely Benign	-0.57	Neutral	0.790	Possibly Damaging	0.353	Benign	4.27	Benign	0.00	Affected			0.3060	0.4030		1	-1	3.4	-26.04
c.2392C>T	P798S 2D AIThe SynGAP1 missense variant P798S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.382	Likely Benign	0.065	Likely Benign	Likely Benign										0.058	Likely Benign	0.14	Neutral	0.818	Possibly Damaging	0.353	Benign	4.28	Benign	0.00	Affected			0.2950	0.4425		1	-1	0.8	-10.04
c.2393C>A	P798Q 2D AIThe SynGAP1 missense variant P798Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P798Q, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.944	Likely Benign	0.074	Likely Benign	Likely Benign										0.068	Likely Benign	-0.53	Neutral	0.988	Probably Damaging	0.780	Possibly Damaging	4.25	Benign	0.00	Affected			0.1290	0.3864		0	-1	-1.9	31.01
c.23T>G	I8S 2D AIThe SynGAP1 missense variant I8S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-1.577	Likely Benign	0.122	Likely Benign	Likely Benign										0.266	Likely Benign	0.18	Neutral	0.107	Benign	0.006	Benign	4.02	Benign	0.00	Affected			0.2726	0.0910		-1	-2	-5.3	-26.08
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	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625					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	0.2325	0.4755		0	1	-0.4	30.03
c.2401G>C	G801R 2D AIThe SynGAP1 missense variant G801R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta data are not available. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-4.226	Likely Benign	0.424	Ambiguous	Likely Benign										0.045	Likely Benign	-0.18	Neutral	0.846	Possibly Damaging	0.624	Possibly Damaging	2.73	Benign	0.64	Tolerated			0.0850	0.3793		-3	-2	-4.1	99.14
c.2401G>T	G801C 2D AIThe SynGAP1 missense variant G801C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-7.542	In-Between	0.125	Likely Benign	Likely Benign										0.156	Likely Benign	-1.83	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	2.67	Benign	0.06	Tolerated			0.1039	0.4021		-3	-3	2.9	46.09
c.2402G>A	G801D 2D AIThe SynGAP1 missense variant G801D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic call comes from polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-5.312	Likely Benign	0.414	Ambiguous	Likely Benign										0.066	Likely Benign	-0.69	Neutral	0.611	Possibly Damaging	0.346	Benign	2.84	Benign	0.25	Tolerated			0.1631	0.1835		1	-1	-3.1	58.04
c.1066C>G	R356G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R356G missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are uncertain and therefore treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-12.305	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	1.02	Ambiguous	0.0	1.80	Ambiguous	1.41	Ambiguous	1.06	Destabilizing	0.271	Likely Benign	-6.20	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.95	Pathogenic	0.08	Tolerated			0.3505	0.3793		-3	-2	4.1	-99.14
c.2402G>C	G801A 2D AIThe SynGAP1 missense variant G801A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). 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. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. **Overall, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-3.747	Likely Benign	0.091	Likely Benign	Likely Benign										0.025	Likely Benign	-0.61	Neutral	0.025	Benign	0.034	Benign	2.83	Benign	0.50	Tolerated			0.3458	0.4681		1	0	2.2	14.03
c.2402G>T	G801V 2D AIThe SynGAP1 missense variant G801V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that G801V is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-4.781	Likely Benign	0.119	Likely Benign	Likely Benign										0.098	Likely Benign	-1.64	Neutral	0.611	Possibly Damaging	0.272	Benign	2.70	Benign	0.11	Tolerated			0.1041	0.4230		-1	-3	4.6	42.08
c.1066C>A	R356S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R356S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and SIFT, whereas the remaining tools—premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for R356S, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-13.059	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	0.79	Ambiguous	0.90	Ambiguous	1.04	Destabilizing	0.292	Likely Benign	-5.28	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.84	Pathogenic	0.07	Tolerated			0.2891	0.4491		0	-1	3.7	-69.11
c.2404G>C	G802R 2D AIThe SynGAP1 missense variant G802R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only SIFT predicts a pathogenic effect, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) likewise predicts likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for G802R, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625											-4.756	Likely Benign	0.504	Ambiguous	Likely Benign										0.072	Likely Benign	-1.05	Neutral	0.259	Benign	0.196	Benign	2.68	Benign	0.01	Affected			0.0995	0.4514		-3	-2	-4.1	99.14
c.2404G>T	G802C 2D AIThe SynGAP1 missense variant G802C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence—including the consensus of multiple independent predictors and the high‑accuracy tools—supports a benign classification for G802C. This conclusion is consistent with the lack of any ClinVar pathogenic annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625											-6.332	Likely Benign	0.127	Likely Benign	Likely Benign										0.127	Likely Benign	-1.60	Neutral	0.983	Probably Damaging	0.819	Possibly Damaging	2.65	Benign	0.00	Affected			0.1426	0.4126		-3	-3	2.9	46.09
c.1064G>T	G355V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G355V is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or unavailable results are reported for FoldX, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-10.111	Likely Pathogenic	0.675	Likely Pathogenic	Likely Benign	1.78	Ambiguous	0.6	0.14	Likely Benign	0.96	Ambiguous	0.53	Ambiguous	0.346	Likely Benign	-7.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.78	Pathogenic	0.04	Affected			0.1221	0.4685		-1	-3	4.6	42.08
c.23T>A	I8N 2D AIThe SynGAP1 missense variant I8N is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of predictors, including the high‑accuracy methods, points to a benign impact. This conclusion is consistent with the absence of any ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-3.979	Likely Benign	0.163	Likely Benign	Likely Benign										0.120	Likely Benign	0.05	Neutral	0.561	Possibly Damaging	0.032	Benign	3.99	Benign	0.00	Affected			0.0803	0.0540		-2	-3	-8.0	0.94
c.239A>T	K80I 2D AIThe SynGAP1 missense variant K80I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic signals and no ClinVar entry to contradict the computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.320	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.083	Likely Benign	-2.54	Deleterious	0.939	Possibly Damaging	0.164	Benign	3.86	Benign	0.00	Affected			0.1095	0.2981		-2	-3	8.4	-15.01
c.2393C>G	P798R 2D AIThe SynGAP1 missense variant P798R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P798R, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.232	Likely Benign	0.162	Likely Benign	Likely Benign										0.065	Likely Benign	-0.83	Neutral	0.976	Probably Damaging	0.780	Possibly Damaging	4.25	Benign	0.00	Affected			0.1397	0.2840		0	-2	-2.9	59.07
c.2395C>A	P799T 2D AIThe SynGAP1 missense variant P799T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P799T, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-5.470	Likely Benign	0.063	Likely Benign	Likely Benign										0.033	Likely Benign	-0.82	Neutral	0.951	Possibly Damaging	0.738	Possibly Damaging	4.24	Benign	0.00	Affected			0.1522	0.5257		0	-1	0.9	3.99
c.2395C>G	P799A 2D AIThe SynGAP1 missense variant P799A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) score; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect for P799A, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-4.660	Likely Benign	0.048	Likely Benign	Likely Benign										0.054	Likely Benign	-0.72	Neutral	0.798	Possibly Damaging	0.489	Possibly Damaging	4.27	Benign	0.00	Affected			0.3488	0.4279		1	-1	3.4	-26.04
c.2395C>T	P799S 2D AIThe SynGAP1 missense variant P799S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for P799S, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-4.635	Likely Benign	0.068	Likely Benign	Likely Benign										0.065	Likely Benign	-0.73	Neutral	0.951	Possibly Damaging	0.593	Possibly Damaging	4.26	Benign	0.00	Affected			0.3411	0.4464		1	-1	0.8	-10.04
c.2396C>A	P799H 2D AIThe SynGAP1 missense variant P799H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign effect. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign classification for P799H, and this conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-5.611	Likely Benign	0.108	Likely Benign	Likely Benign										0.089	Likely Benign	-0.80	Neutral	0.999	Probably Damaging	0.933	Probably Damaging	4.20	Benign	0.00	Affected			0.1684	0.4192		0	-2	-1.6	40.02
c.2396C>G	P799R 2D AIThe SynGAP1 missense variant P799R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) likewise indicates benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-5.100	Likely Benign	0.141	Likely Benign	Likely Benign										0.029	Likely Benign	-0.49	Neutral	0.029	Benign	0.022	Benign	4.27	Benign	0.00	Affected			0.1425	0.2905		0	-2	-2.9	59.07
c.2396C>T	P799L 2D AIThe SynGAP1 missense variant P799L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P799L, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-5.296	Likely Benign	0.090	Likely Benign	Likely Benign										0.043	Likely Benign	-0.93	Neutral	0.905	Possibly Damaging	0.670	Possibly Damaging	4.27	Benign	0.00	Affected			0.2078	0.6285		-3	-3	5.4	16.04
c.2398G>A	G800S 2D AIThe SynGAP1 missense variant G800S is reported as “Likely Benign” by the SGM‑Consensus method and is absent from ClinVar and gnomAD. All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625											-3.572	Likely Benign	0.088	Likely Benign	Likely Benign										0.083	Likely Benign	-0.69	Neutral	0.292	Benign	0.157	Benign	2.78	Benign	0.60	Tolerated			0.2375	0.4923		1	0	-0.4	30.03
c.2398G>C	G800R 2D AIThe SynGAP1 missense variant G800R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625											-3.613	Likely Benign	0.405	Ambiguous	Likely Benign										0.147	Likely Benign	-0.27	Neutral	0.003	Benign	0.004	Benign	2.84	Benign	0.17	Tolerated			0.0868	0.3835		-3	-2	-4.1	99.14
c.2398G>T	G800C 2D AIThe SynGAP1 missense variant G800C is not reported in ClinVar and has no allele in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of a ClinVar pathogenic annotation. Based on the aggregate predictions, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625											-7.074	In-Between	0.129	Likely Benign	Likely Benign										0.144	Likely Benign	-1.53	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	2.70	Benign	0.15	Tolerated			0.1102	0.4189		-3	-3	2.9	46.09
c.2399G>T	G800V 2D AIThe SynGAP1 missense variant G800V is predicted to be benign by all evaluated in‑silico tools. ClinVar contains no entry for this variant, and it is not reported in gnomAD. Consensus predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625											-4.890	Likely Benign	0.113	Likely Benign	Likely Benign										0.078	Likely Benign	-1.24	Neutral	0.451	Benign	0.157	Benign	2.73	Benign	0.25	Tolerated			0.1130	0.4198		-1	-3	4.6	42.08
c.239A>C	K80T 2D AIThe SynGAP1 missense variant K80T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized prediction is uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-4.987	Likely Benign	0.830	Likely Pathogenic	Ambiguous										0.072	Likely Benign	-1.60	Neutral	0.588	Possibly Damaging	0.036	Benign	3.89	Benign	0.00	Affected			0.2139	0.2321		0	-1	3.2	-27.07
c.1064G>C	G355A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G355A missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. FoldX and Foldetta are uncertain and therefore not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta is uncertain. Consequently, the overall prediction leans toward a benign effect, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-5.431	Likely Benign	0.245	Likely Benign	Likely Benign	0.88	Ambiguous	0.6	0.46	Likely Benign	0.67	Ambiguous	0.49	Likely Benign	0.286	Likely Benign	-4.80	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.03	Affected			0.4111	0.5045		1	0	2.2	14.03
c.2447C>G	S816C 2D AIThe SynGAP1 missense variant S816C has no ClinVar record and is not present in gnomAD. Functional prediction tools fall into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the evidence is mixed, with an equal split between benign and pathogenic calls among general predictors and conflicting outcomes from the two high‑accuracy tools. The variant is most likely pathogenic based on the predominance of pathogenic predictions, and this assessment does not contradict ClinVar status, which currently has no entry for S816C. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-7.998	In-Between	0.605	Likely Pathogenic	Likely Benign										0.246	Likely Benign	-2.75	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	2.59	Benign	0.06	Tolerated			0.1167	0.5472		0	-1	3.3	16.06
c.2455G>A	A819T 2D AIThe SynGAP1 missense variant A819T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign) and Foldetta data are unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy tool predicts benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-3.421	Likely Benign	0.675	Likely Pathogenic	Likely Benign										0.287	Likely Benign	-2.23	Neutral	0.998	Probably Damaging	0.963	Probably Damaging	2.29	Pathogenic	0.01	Affected			0.1443	0.7583		1	0	-2.5	30.03
c.1046C>G	P349R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Rosetta. Uncertain or inconclusive results come from FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P349R. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-14.001	Likely Pathogenic	0.791	Likely Pathogenic	Ambiguous	0.99	Ambiguous	0.1	2.15	Destabilizing	1.57	Ambiguous	0.93	Ambiguous	0.335	Likely Benign	-7.22	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.55	Pathogenic	0.01	Affected			0.1395	0.3009		0	-2	-2.9	59.07
c.2455G>C	A819P 2D AIThe SynGAP1 missense variant A819P is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A819P, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-5.542	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.342	Likely Benign	-3.18	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.17	Pathogenic	0.01	Affected			0.1920	0.5753		1	-1	-3.4	26.04
c.2455G>T	A819S 2D AIThe SynGAP1 missense variant A819S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A819S, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-3.420	Likely Benign	0.331	Likely Benign	Likely Benign										0.199	Likely Benign	-1.49	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.33	Pathogenic	0.27	Tolerated			0.2729	0.6404		1	1	-2.6	16.00
c.2456C>A	A819E 2D AIThe SynGAP1 missense variant A819E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-7.333	In-Between	0.982	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-2.85	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.19	Pathogenic	0.00	Affected			0.1189	0.2037		0	-1	-5.3	58.04
c.1046C>A	P349Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 P349Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-10.545	Likely Pathogenic	0.508	Ambiguous	Likely Benign	0.98	Ambiguous	0.1	1.87	Ambiguous	1.43	Ambiguous	0.91	Ambiguous	0.345	Likely Benign	-6.40	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.54	Pathogenic	0.06	Tolerated			0.1480	0.4766		0	-1	-1.9	31.01
c.2456C>G	A819G 2D AIThe SynGAP1 missense variant A819G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (six benign vs three pathogenic) support a benign classification. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-5.730	Likely Benign	0.714	Likely Pathogenic	Likely Benign										0.116	Likely Benign	-2.17	Neutral	0.104	Benign	0.121	Benign	2.29	Pathogenic	0.03	Affected			0.2363	0.5396		1	0	-2.2	-14.03
c.1045C>T	P349S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P349S missense variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are inconclusive or uncertain are FoldX, ESM1b, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, predict a pathogenic effect. Thus, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000					Uncertain		1				-7.654	In-Between	0.217	Likely Benign	Likely Benign	1.92	Ambiguous	0.1	2.28	Destabilizing	2.10	Destabilizing	0.87	Ambiguous	0.277	Likely Benign	-6.13	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.66	Pathogenic	0.06	Tolerated	3.37	25	0.3771	0.5756		1	-1	0.8	-10.04	194.9	-18.1	-0.1	0.0	0.2	0.1	X						X	Potentially Pathogenic	The cyclic pyrrolidine side chain of Pro349, located at the end of an anti-parallel β sheet strand (res. Gly341-Pro349), allows the strand to end and make a tight turn before a short α helical section within a loop connecting to another β strand (res. Thr359-Pro364). In the variant simulations, the hydroxyl group of Ser349 forms a hydrogen bond with the backbone amide group of Ala351 in the short helical section. Conversely, the backbone amide group of Ser349 (absent in proline) does not form any intra-protein hydrogen bonds. However, the β strand end connects to the α helical section in a more stable and consistent manner compared to the WT. Although the residue swap does not cause major adverse effects on the protein structure in the simulations, it is possible that the tight turn at the β strand end could not be created during folding without the presence of proline.
c.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.			0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625					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			0.2352	0.0704		-2	-2	-2.2	-49.07
c.1045C>G	P349A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, with the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other stability or pathogenicity scores are available. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-8.663	Likely Pathogenic	0.202	Likely Benign	Likely Benign	1.37	Ambiguous	0.0	1.68	Ambiguous	1.53	Ambiguous	0.76	Ambiguous	0.257	Likely Benign	-6.01	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.01	Affected			0.3789	0.5505		1	-1	3.4	-26.04
c.2458T>G	Y820D 2D AIThe SynGAP1 missense variant Y820D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that Y820D is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-10.497	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-2.77	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.73	Benign	0.08	Tolerated			0.4113	0.0704		-4	-3	-2.2	-48.09
c.2459A>C	Y820S 2D AIThe SynGAP1 missense variant Y820S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for Y820S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-7.094	In-Between	0.723	Likely Pathogenic	Likely Benign										0.101	Likely Benign	-1.79	Neutral	0.999	Probably Damaging	0.951	Probably Damaging	2.80	Benign	0.22	Tolerated			0.5166	0.2291	Weaken	-3	-2	0.5	-76.10
c.1046C>T	P349L 2D AIThe SynGAP1 missense variant P349L is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy methods give conflicting results: AlphaMissense‑Optimized reports a benign outcome, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Other stability‑based predictors (FoldX, Rosetta, premPS) are also inconclusive. Overall, the preponderance of evidence from the consensus of multiple in‑silico tools points to a pathogenic effect for P349L. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-11.734	Likely Pathogenic	0.650	Likely Pathogenic	Likely Benign	0.70	Ambiguous	0.6	1.17	Ambiguous	0.94	Ambiguous	0.57	Ambiguous	0.326	Likely Benign	-8.04	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.2222	0.6867		-3	-3	5.4	16.04
c.2453C>G	P818R 2D AIThe SynGAP1 missense variant P818R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. ESM1b is uncertain and does not contribute to a consensus. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Pathogenic” designation. AlphaMissense‑Optimized independently predicts pathogenicity, while Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-7.267	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.374	Likely Benign	-5.12	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.03	Affected			0.1499	0.4547		0	-2	-2.9	59.07
c.2447C>T	S816F 2D AIThe SynGAP1 missense variant S816F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. When predictions are grouped, two tools predict benign and six predict pathogenic. High‑accuracy assessment further supports a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy predictors indicates that S816F is most likely pathogenic, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-8.804	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.232	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.59	Benign	0.03	Affected			0.0605	0.5014		-3	-2	3.6	60.10
c.2449T>A	S817T 2D AIThe SynGAP1 missense variant S817T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign, and Foldetta results are unavailable. Overall, the balance of evidence from both general and high‑accuracy predictors points to a benign impact for S817T. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-6.544	Likely Benign	0.492	Ambiguous	Likely Benign										0.157	Likely Benign	-1.95	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.43	Pathogenic	0.00	Affected			0.1622	0.6482		1	1	0.1	14.03
c.2449T>C	S817P 2D AIThe SynGAP1 missense variant S817P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus score indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-4.633	Likely Benign	0.724	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-3.26	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.39	Pathogenic	0.00	Affected			0.2272	0.6023		1	-1	-0.8	10.04
c.1048G>T	V350L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No other tools provide conflicting evidence. Based on the preponderance of predictions, V350L is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-5.941	Likely Benign	0.238	Likely Benign	Likely Benign	-1.31	Ambiguous	0.1	-0.34	Likely Benign	-0.83	Ambiguous	0.36	Likely Benign	0.042	Likely Benign	-1.63	Neutral	0.068	Benign	0.022	Benign	2.37	Pathogenic	0.27	Tolerated			0.1173	0.4958		2	1	-0.4	14.03
c.2449T>G	S817A 2D AIThe SynGAP1 missense variant S817A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign, while Foldetta results are unavailable. Overall, the majority of high‑confidence predictions indicate a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-6.321	Likely Benign	0.429	Ambiguous	Likely Benign										0.116	Likely Benign	-1.86	Neutral	0.977	Probably Damaging	0.846	Possibly Damaging	2.45	Pathogenic	0.00	Affected			0.5207	0.5866	Strenghten	1	1	2.6	-16.00
c.244C>A	L82M 2D AIThe SynGAP1 missense variant L82M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized prediction is uncertain, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-4.608	Likely Benign	0.888	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-0.68	Neutral	0.939	Possibly Damaging	0.114	Benign	3.67	Benign	0.00	Affected			0.0744	0.3278		4	2	-1.9	18.03
c.2450C>T	S817L 2D AIThe SynGAP1 missense variant S817L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-7.612	In-Between	0.659	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.90	Deleterious	0.997	Probably Damaging	0.945	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1226	0.5662		-3	-2	4.6	26.08
c.2452C>A	P818T 2D AIThe SynGAP1 missense variant P818T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.864	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.265	Likely Benign	-4.58	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.01	Pathogenic	0.02	Affected			0.1797	0.6453		0	-1	0.9	3.99
c.1048G>C	V350L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only FATHMM predicts a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign status. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as uncertain. No other tools provide conflicting evidence. Based on the preponderance of benign predictions and the lack of pathogenic support, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-5.941	Likely Benign	0.238	Likely Benign	Likely Benign	-1.31	Ambiguous	0.1	-0.34	Likely Benign	-0.83	Ambiguous	0.36	Likely Benign	0.042	Likely Benign	-1.63	Neutral	0.068	Benign	0.022	Benign	2.37	Pathogenic	0.27	Tolerated			0.1173	0.4958		2	1	-0.4	14.03
c.2452C>G	P818A 2D AIThe SynGAP1 missense variant P818A is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 HumVar, SIFT, and ESM1b, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default. When the predictions are grouped by consensus, four tools favor benign and four favor pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Taken together, the preponderance of evidence from both consensus and high‑accuracy tools indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.084	Likely Benign	0.820	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-4.37	Deleterious	0.543	Possibly Damaging	0.306	Benign	2.15	Pathogenic	0.06	Tolerated			0.3574	0.5724		1	-1	3.4	-26.04
c.1048G>A	V350M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The remaining tools (FoldX, premPS, ESM1b) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as benign. Taken together, the majority of evidence supports a benign classification. There is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-7.493	In-Between	0.273	Likely Benign	Likely Benign	-0.65	Ambiguous	0.1	0.40	Likely Benign	-0.13	Likely Benign	0.69	Ambiguous	0.075	Likely Benign	-1.95	Neutral	0.868	Possibly Damaging	0.383	Benign	1.63	Pathogenic	0.06	Tolerated			0.1005	0.4359		2	1	-2.3	32.06
c.2453C>A	P818Q 2D AIThe SynGAP1 missense variant P818Q is not listed in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P818Q is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.855	Likely Benign	0.969	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-4.07	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.27	Tolerated			0.1569	0.5456		0	-1	-1.9	31.01
c.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		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625					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	0.3177	0.1915		0	-2	3.8	-60.04
c.2459A>T	Y820F 2D AIThe SynGAP1 missense variant Y820F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for Y820F, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-4.686	Likely Benign	0.301	Likely Benign	Likely Benign										0.111	Likely Benign	-1.67	Neutral	0.990	Probably Damaging	0.893	Possibly Damaging	2.69	Benign	0.21	Tolerated			0.2398	0.2636		7	3	4.1	-16.00
c.245T>A	L82Q 2D AIThe SynGAP1 missense variant L82Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction. Foldetta results are unavailable. Overall, the majority of conventional tools lean toward benign, and the SGM Consensus supports this, but the AlphaMissense‑Optimized prediction introduces a pathogenic signal. Consequently, the variant is most likely benign based on the prevailing evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-7.576	In-Between	0.987	Likely Pathogenic	Likely Pathogenic										0.079	Likely Benign	-2.16	Neutral	0.939	Possibly Damaging	0.114	Benign	3.71	Benign	0.00	Affected			0.1150	0.0790		-2	-2	-7.3	14.97
c.2465C>A	T822K 2D AIThe SynGAP1 missense variant T822K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of conventional tools lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction contradicts this. Because ClinVar has no entry for this variant, there is no existing clinical classification to conflict with; thus, the variant is most likely benign based on the preponderance of evidence, though high‑accuracy predictions remain inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-1.814	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-2.25	Neutral	1.000	Probably Damaging	0.988	Probably Damaging	2.51	Benign	0.07	Tolerated			0.1369	0.3552		0	-1	-3.2	27.07
c.2465C>G	T822R 2D AIThe SynGAP1 missense variant T822R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (five pathogenic versus three benign predictions) suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											0.414	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-2.74	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	2.50	Benign	0.05	Affected			0.1182	0.3439		-1	-1	-3.8	55.08
c.1043T>A	V348E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348E is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among the majority of tools, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for V348E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-11.135	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.1	2.20	Destabilizing	2.31	Destabilizing	2.14	Destabilizing	0.470	Likely Benign	-5.26	Deleterious	0.989	Probably Damaging	0.637	Possibly Damaging	1.56	Pathogenic	0.01	Affected			0.1089	0.1922		-2	-2	-7.7	29.98
c.2467A>C	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools points to a pathogenic effect for S823R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.293	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2467A>G	S823G 2D AIThe SynGAP1 missense variant S823G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the Foldetta stability analysis is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.034	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.2855	0.5287		1	0	0.4	-30.03
c.2467A>T	S823C 2D AIThe SynGAP1 missense variant S823C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability prediction is available, so it does not contribute to the assessment. Overall, the preponderance of evidence points to a pathogenic effect for S823C, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.881	In-Between	0.911	Likely Pathogenic	Ambiguous										0.332	Likely Benign	-3.80	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.1019	0.6137		0	-1	3.3	16.06
c.2468G>A	S823N 2D AIThe SynGAP1 missense variant S823N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.880	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-1.76	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1370	0.5172		1	1	-2.7	27.03
c.1042G>T	V348L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No other high‑confidence tools provide conflicting evidence. Based on the preponderance of predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-4.842	Likely Benign	0.270	Likely Benign	Likely Benign	-0.58	Ambiguous	0.0	0.04	Likely Benign	-0.27	Likely Benign	0.24	Likely Benign	0.072	Likely Benign	-0.75	Neutral	0.264	Benign	0.030	Benign	1.89	Pathogenic	0.62	Tolerated			0.1088	0.4953		2	1	-0.4	14.03
c.2468G>C	S823T 2D AIThe SynGAP1 missense variant S823T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two benign, two pathogenic). AlphaMissense‑Optimized predicts benign, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.036	Likely Benign	0.717	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.02	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.05	Pathogenic	0.00	Affected			0.1453	0.6580		1	1	0.1	14.03
c.2468G>T	S823I 2D AIThe SynGAP1 missense variant S823I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only REVEL predicts a benign outcome, while ESM1b remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.332	In-Between	0.990	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-4.26	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0964	0.5848		-1	-2	5.3	26.08
c.2469C>A	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2469C>G	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2464A>T	T822S 2D AIThe SynGAP1 missense variant T822S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T822S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-1.710	Likely Benign	0.655	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-0.54	Neutral	0.998	Probably Damaging	0.949	Probably Damaging	3.08	Benign	0.74	Tolerated			0.3794	0.4547		1	1	-0.1	-14.03
c.2464A>G	T822A 2D AIThe SynGAP1 T822A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus (majority vote) remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-3.695	Likely Benign	0.788	Likely Pathogenic	Ambiguous										0.122	Likely Benign	-1.55	Neutral	0.987	Probably Damaging	0.891	Possibly Damaging	2.60	Benign	0.17	Tolerated			0.4566	0.4456		1	0	2.5	-30.03
c.245T>G	L82R 2D AIThe SynGAP1 missense variant L82R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, and this is not contradicted by any ClinVar annotation. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-6.345	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.077	Likely Benign	-2.18	Neutral	0.939	Possibly Damaging	0.114	Benign	3.67	Benign	0.00	Affected			0.1338	0.0590		-3	-2	-8.3	43.03
c.1045C>A	P349T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score (which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools with inconclusive results are AlphaMissense‑Default, FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-9.736	Likely Pathogenic	0.420	Ambiguous	Likely Benign	1.37	Ambiguous	0.1	2.56	Destabilizing	1.97	Ambiguous	0.76	Ambiguous	0.246	Likely Benign	-6.12	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.57	Pathogenic	0.07	Tolerated			0.1615	0.6238		0	-1	0.9	3.99
c.2461T>A	C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-0.425	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-0.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.91	Benign	1.00	Tolerated			0.5284	0.2012	Weaken	0	-1	-3.3	-16.06
c.2461T>C	C821R 2D AIThe SynGAP1 missense variant C821R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, while three suggest benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-3.997	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.1944	0.1746		-4	-3	-7.0	53.05
c.2461T>G	C821G 2D AIThe SynGAP1 missense variant C821G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.613	Likely Benign	0.910	Likely Pathogenic	Ambiguous										0.187	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.05	Affected			0.3287	0.2747		-3	-3	-2.9	-46.09
c.2462G>A	C821Y 2D AIThe SynGAP1 missense variant C821Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools support pathogenicity while three support benignity, and no high‑accuracy consensus contradicts this trend. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-1.007	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.01	Affected			0.1288	0.3187		0	-2	-3.8	60.04
c.1043T>G	V348G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the lack of a benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-12.793	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.2	5.70	Destabilizing	4.84	Destabilizing	2.23	Destabilizing	0.419	Likely Benign	-6.18	Deleterious	0.637	Possibly Damaging	0.989	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.2229	0.2082		-1	-3	-4.6	-42.08
c.2462G>C	C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-0.425	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.314	Likely Benign	-0.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.91	Benign	1.00	Tolerated			0.5284	0.2012	Weaken	0	-1	-3.3	-16.06
c.2462G>T	C821F 2D AIThe SynGAP1 missense variant C821F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											0.971	Likely Benign	0.924	Likely Pathogenic	Ambiguous										0.338	Likely Benign	-3.33	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.01	Affected			0.1504	0.3505		-4	-2	0.3	44.04
c.2463C>G	C821W 2D AIThe SynGAP1 missense variant C821W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.843	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.201	Likely Benign	-3.30	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.64	Benign	0.01	Affected			0.1742	0.3268		-8	-2	-3.4	83.07
c.1043T>C	V348A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further highlight the discrepancy: AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as pathogenic. Taken together, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict ClinVar status, which currently has no entry for V348A. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-9.993	Likely Pathogenic	0.767	Likely Pathogenic	Likely Benign	2.46	Destabilizing	0.1	3.13	Destabilizing	2.80	Destabilizing	2.23	Destabilizing	0.175	Likely Benign	-3.42	Deleterious	0.622	Possibly Damaging	0.152	Benign	1.59	Pathogenic	0.14	Tolerated			0.3223	0.2437		0	0	-2.4	-28.05
c.2464A>C	T822P 2D AIThe SynGAP1 missense variant T822P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T822P. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-3.961	Likely Benign	0.737	Likely Pathogenic	Likely Benign										0.145	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.50	Benign	0.09	Tolerated			0.2437	0.5044		0	-1	-0.9	-3.99
c.2470A>C	S824R 2D AIThe SynGAP1 missense variant S824R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign interpretation, but the split in high‑accuracy tools introduces uncertainty. The variant is therefore most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-5.589	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.61	Benign	0.23	Tolerated			0.1096	0.4255		0	-1	-3.7	69.11
c.1055C>G	T352S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.670	Likely Benign	0.062	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	0.26	Likely Benign	0.09	Likely Benign	-0.01	Likely Benign	0.104	Likely Benign	0.57	Neutral	0.002	Benign	0.002	Benign	1.81	Pathogenic	1.00	Tolerated			0.3583	0.4880		1	1	-0.1	-14.03
c.2429G>T	R810L 2D AIThe SynGAP1 R810L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in‑silico predictors points to a pathogenic impact for R810L. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-7.172	In-Between	0.834	Likely Pathogenic	Ambiguous										0.338	Likely Benign	-4.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			0.2019	0.5271		-3	-2	8.3	-43.03
c.242T>A	L81Q 2D AIThe SynGAP1 missense variant L81Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-5.055	Likely Benign	0.517	Ambiguous	Likely Benign										0.052	Likely Benign	-1.22	Neutral	0.919	Possibly Damaging	0.226	Benign	3.93	Benign	0.00	Affected			0.1046	0.0888		-2	-2	-7.3	14.97
c.1232T>A	I411N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-14.426	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.00	Destabilizing	0.1	3.71	Destabilizing	3.36	Destabilizing	2.16	Destabilizing	0.556	Likely Pathogenic	-6.42	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.29	Benign	0.00	Affected			0.0738	0.0700		-2	-3	-8.0	0.94
c.242T>G	L81R 2D AIThe SynGAP1 missense variant L81R is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors shows a split: benign calls from REVEL, PROVEAN, polyPhen2_HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen2_HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability assessment is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-4.451	Likely Benign	0.639	Likely Pathogenic	Likely Benign										0.053	Likely Benign	-1.22	Neutral	0.919	Possibly Damaging	0.226	Benign	3.94	Benign	0.00	Affected			0.1179	0.0688		-3	-2	-8.3	43.03
c.2431C>A	P811T 2D AIThe SynGAP1 missense variant P811T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for P811T, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.329	Likely Benign	0.488	Ambiguous	Likely Benign										0.119	Likely Benign	-1.94	Neutral	0.991	Probably Damaging	0.864	Possibly Damaging	2.77	Benign	0.03	Affected			0.1679	0.6095		0	-1	0.9	3.99
c.2431C>G	P811A 2D AIThe SynGAP1 missense variant P811A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence supports a benign classification for P811A, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.120	Likely Benign	0.287	Likely Benign	Likely Benign										0.104	Likely Benign	-2.11	Neutral	0.939	Possibly Damaging	0.670	Possibly Damaging	2.76	Benign	0.57	Tolerated			0.3763	0.5485		1	-1	3.4	-26.04
c.2431C>T	P811S 2D AIThe SynGAP1 missense variant P811S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, and AlphaMissense‑Default remains uncertain. No Foldetta stability assessment is available, so it does not contribute to the evidence. Overall, the preponderance of evidence points to a benign effect for P811S, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-4.733	Likely Benign	0.474	Ambiguous	Likely Benign										0.128	Likely Benign	-1.28	Neutral	0.982	Probably Damaging	0.824	Possibly Damaging	2.79	Benign	0.78	Tolerated			0.3656	0.5960		1	-1	0.8	-10.04
c.2432C>A	P811Q 2D AIThe SynGAP1 missense variant P811Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.145	Likely Benign	0.431	Ambiguous	Likely Benign										0.138	Likely Benign	-2.38	Neutral	0.982	Probably Damaging	0.875	Possibly Damaging	2.78	Benign	0.01	Affected			0.1523	0.5338		0	-1	-1.9	31.01
c.1052C>A	A351D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A351D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and FATHMM; AlphaMissense‑Default and ESM1b are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward pathogenic due to two pathogenic and two uncertain calls. Overall, the majority of tools predict a benign outcome, and this does not contradict the lack of ClinVar annotation. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-7.917	In-Between	0.543	Ambiguous	Likely Benign	-0.02	Likely Benign	0.0	-0.12	Likely Benign	-0.07	Likely Benign	0.49	Likely Benign	0.114	Likely Benign	-3.61	Deleterious	0.842	Possibly Damaging	0.321	Benign	1.77	Pathogenic	0.11	Tolerated			0.1535	0.1386		0	-2	-5.3	44.01
c.2432C>G	P811R 2D AIThe SynGAP1 missense variant P811R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT; AlphaMissense‑Default remains uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as benign, while Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the preponderance of evidence points to a benign impact for P811R, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.273	Likely Benign	0.557	Ambiguous	Likely Benign										0.065	Likely Benign	-2.69	Deleterious	0.100	Benign	0.066	Benign	2.73	Benign	0.01	Affected			0.1448	0.3817		0	-2	-2.9	59.07
c.1051G>T	A351S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A351S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy methods—AlphaMissense‑Optimized, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (integrating FoldX‑MD and Rosetta)—all report benign or likely benign. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely benign; this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-4.823	Likely Benign	0.073	Likely Benign	Likely Benign	0.24	Likely Benign	0.0	0.25	Likely Benign	0.25	Likely Benign	0.27	Likely Benign	0.016	Likely Benign	-1.42	Neutral	0.080	Benign	0.023	Benign	1.88	Pathogenic	0.13	Tolerated			0.2558	0.5334		1	1	-2.6	16.00
c.2432C>T	P811L 2D AIThe SynGAP1 P811L missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. AlphaMissense‑Default is uncertain. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans toward benign (2 benign vs. 1 pathogenic, 1 uncertain). AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from high‑accuracy tools and consensus methods indicates that P811L is most likely benign. This assessment does not contradict ClinVar status, as the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-6.184	Likely Benign	0.491	Ambiguous	Likely Benign										0.150	Likely Benign	-3.98	Deleterious	0.982	Probably Damaging	0.824	Possibly Damaging	2.71	Benign	0.01	Affected			0.2327	0.6621		-3	-3	5.4	16.04
c.2429G>C	R810P 2D AIThe SynGAP1 missense variant R810P is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic impact for R810P. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-4.120	Likely Benign	0.779	Likely Pathogenic	Likely Benign										0.316	Likely Benign	-4.08	Deleterious	1.000	Probably Damaging	0.977	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.2307	0.5478		0	-2	2.9	-59.07
c.1052C>G	A351G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A351G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs two pathogenic), and Foldetta is uncertain. Taken together, the majority of available predictions lean toward a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-4.983	Likely Benign	0.089	Likely Benign	Likely Benign	0.39	Likely Benign	0.0	1.04	Ambiguous	0.72	Ambiguous	0.55	Ambiguous	0.041	Likely Benign	-2.53	Deleterious	0.688	Possibly Damaging	0.138	Benign	1.77	Pathogenic	0.04	Affected			0.2298	0.4737		1	0	-2.2	-14.03
c.2425A>T	S809C 2D AIThe SynGAP1 missense variant S809C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-8.186	Likely Pathogenic	0.221	Likely Benign	Likely Benign										0.145	Likely Benign	-1.99	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.49	Pathogenic	0.01	Affected			0.1088	0.6174		0	-1	3.3	16.06
c.1054A>T	T352S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.670	Likely Benign	0.062	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	0.26	Likely Benign	0.09	Likely Benign	-0.01	Likely Benign	0.098	Likely Benign	0.57	Neutral	0.002	Benign	0.002	Benign	1.81	Pathogenic	1.00	Tolerated			0.3583	0.4880		1	1	-0.1	-14.03
c.2426G>A	S809N 2D AIThe SynGAP1 missense variant S809N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for S809N, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-5.308	Likely Benign	0.341	Ambiguous	Likely Benign										0.079	Likely Benign	-1.12	Neutral	0.784	Possibly Damaging	0.316	Benign	2.51	Benign	0.04	Affected			0.1363	0.5028		1	1	-2.7	27.03
c.2426G>C	S809T 2D AIThe SynGAP1 missense variant S809T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign outcome. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-3.865	Likely Benign	0.091	Likely Benign	Likely Benign										0.076	Likely Benign	0.68	Neutral	0.003	Benign	0.010	Benign	2.95	Benign	0.82	Tolerated			0.1430	0.6617		1	1	0.1	14.03
c.2426G>T	S809I 2D AIThe SynGAP1 missense variant S809I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from standard in silico predictors shows a split: six tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized) predict a benign effect, while two (SIFT, AlphaMissense‑Default) predict pathogenicity; ESM1b is uncertain. High‑accuracy assessment further supports a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign classification, and Foldetta data are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-7.708	In-Between	0.632	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.93	Neutral	0.065	Benign	0.022	Benign	2.50	Benign	0.01	Affected			0.1039	0.5984		-1	-2	5.3	26.08
c.2427C>A	S809R 2D AIThe SynGAP1 missense variant S809R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into three groups: benign predictions from REVEL, PROVEAN, and FATHMM; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; and uncertain predictions from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign. Protein‑folding stability analysis with Foldetta is unavailable. Overall, the balance of evidence, particularly the benign consensus from high‑accuracy tools, suggests the variant is most likely benign, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-7.062	In-Between	0.935	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-1.50	Neutral	0.784	Possibly Damaging	0.472	Possibly Damaging	2.51	Benign	0.01	Affected			0.0954	0.3702		0	-1	-3.7	69.11
c.1054A>G	T352A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic, while Rosetta remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, integrating FoldX‑MD (benign) and Rosetta (uncertain), reports benign stability. Overall, the preponderance of evidence indicates that T352A is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.952	Likely Benign	0.055	Likely Benign	Likely Benign	0.12	Likely Benign	0.0	0.50	Ambiguous	0.31	Likely Benign	0.45	Likely Benign	0.032	Likely Benign	-1.09	Neutral	0.031	Benign	0.024	Benign	1.73	Pathogenic	0.29	Tolerated			0.4341	0.4938		1	0	2.5	-30.03
c.2427C>G	S809R 2D AIThe SynGAP1 missense variant S809R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into three groups: benign predictions from REVEL, PROVEAN, and FATHMM; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; and uncertain predictions from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign. Protein‑folding stability analysis with Foldetta is unavailable. Overall, the balance of evidence, particularly the benign consensus from high‑accuracy tools, suggests the variant is most likely benign, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-7.062	In-Between	0.935	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-1.50	Neutral	0.784	Possibly Damaging	0.472	Possibly Damaging	2.51	Benign	0.01	Affected			0.0954	0.3702		0	-1	-3.7	69.11
c.2428C>A	R810S 2D AIThe SynGAP1 R810S missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that R810S is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-5.996	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.204	Likely Benign	-3.20	Deleterious	0.996	Probably Damaging	0.900	Possibly Damaging	2.44	Pathogenic	0.01	Affected			0.3152	0.4556		0	-1	3.7	-69.11
c.1054A>C	T352P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T352P has no ClinVar entry and is not reported in gnomAD. Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, FATHMM, and Rosetta. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Overall, the balance of evidence favors a benign interpretation; this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-3.562	Likely Benign	0.138	Likely Benign	Likely Benign	1.04	Ambiguous	0.1	2.57	Destabilizing	1.81	Ambiguous	0.51	Ambiguous	0.159	Likely Benign	-2.31	Neutral	0.627	Possibly Damaging	0.196	Benign	1.72	Pathogenic	0.20	Tolerated			0.2244	0.5968		0	-1	-0.9	-3.99
c.2428C>G	R810G 2D AISynGAP1 missense variant R810G is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: a single benign call from REVEL, and six pathogenic calls from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools (ESM1b and AlphaMissense‑Optimized) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic impact for R810G, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-7.190	In-Between	0.828	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-3.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			0.3686	0.4207		-3	-2	4.1	-99.14
c.1052C>T	A351V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A351V is not reported in ClinVar and is absent from gnomAD. Computational predictions cluster into two groups: benign (REVEL, FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen2_HumVar) and pathogenic (PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, FATHMM, SGM‑Consensus). High‑accuracy tools give a mixed signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence leans toward a benign effect, but the presence of several pathogenic predictions introduces uncertainty. The variant is most likely benign based on the current computational data, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-9.002	Likely Pathogenic	0.124	Likely Benign	Likely Benign	0.09	Likely Benign	0.0	0.19	Likely Benign	0.14	Likely Benign	0.29	Likely Benign	0.052	Likely Benign	-2.84	Deleterious	0.915	Possibly Damaging	0.321	Benign	1.66	Pathogenic	0.03	Affected			0.1140	0.6565		0	0	2.4	28.05
c.2434C>A	P812T 2D AIThe SynGAP1 missense variant P812T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.956	Likely Benign	0.524	Ambiguous	Likely Benign										0.105	Likely Benign	-1.50	Neutral	0.994	Probably Damaging	0.927	Probably Damaging	2.73	Benign	0.04	Affected			0.1413	0.6114		0	-1	0.9	3.99
c.2434C>G	P812A 2D AIThe SynGAP1 missense variant P812A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.113	Likely Benign	0.275	Likely Benign	Likely Benign										0.137	Likely Benign	-1.49	Neutral	0.989	Probably Damaging	0.869	Possibly Damaging	2.75	Benign	0.08	Tolerated			0.3555	0.5350		1	-1	3.4	-26.04
c.1051G>C	A351P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A351P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are Foldetta, PROVEAN, SIFT, FATHMM, and Rosetta. FoldX and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the lack of ClinVar reporting; thus the variant is most likely benign rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-6.559	Likely Benign	0.147	Likely Benign	Likely Benign	-0.89	Ambiguous	0.2	6.19	Destabilizing	2.65	Destabilizing	0.62	Ambiguous	0.051	Likely Benign	-3.08	Deleterious	0.016	Benign	0.007	Benign	1.67	Pathogenic	0.03	Affected			0.1862	0.5472		1	-1	-3.4	26.04
c.2441C>T	A814V 2D AIThe SynGAP1 missense variant A814V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available, so these do not influence the overall inference. Overall, the preponderance of evidence points to a benign effect for A814V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-4.147	Likely Benign	0.374	Ambiguous	Likely Benign										0.119	Likely Benign	-0.14	Neutral	0.811	Possibly Damaging	0.489	Possibly Damaging	2.71	Benign	0.83	Tolerated			0.1088	0.6197		0	0	2.4	28.05
c.2443C>A	R815S 2D AISynGAP1 R815S is listed in ClinVar as Benign (ID 3645150.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus as Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of predictions lean toward pathogenicity, whereas the consensus and high‑accuracy tools suggest benignity. Thus, the variant is most likely pathogenic based on the prevailing predictions, contradicting its ClinVar benign designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Benign		1				-7.324	In-Between	0.950	Likely Pathogenic	Ambiguous										0.138	Likely Benign	-1.86	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.02	Affected			0.2937	0.4164		0	-1	3.7	-69.11
c.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	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					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	0.3481	0.4015		-3	-2	4.1	-99.14
c.104T>A	V35D 2D AIThe SynGAP1 missense variant V35D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.613573	Disordered	0.434838	Uncertain	0.360	0.851	0.375											-4.232	Likely Benign	0.321	Likely Benign	Likely Benign										0.125	Likely Benign	-0.42	Neutral	0.824	Possibly Damaging	0.828	Possibly Damaging	4.18	Benign	0.00	Affected			0.1540	0.1547		-2	-3	-7.7	15.96
c.1049T>G	V350G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350G lies in the C2 domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumDiv, and AlphaMissense‑Optimized. The remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All predictions are available and consistent. Based on the preponderance of pathogenic calls, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-12.267	Likely Pathogenic	0.597	Likely Pathogenic	Likely Benign	2.57	Destabilizing	0.0	4.25	Destabilizing	3.41	Destabilizing	1.93	Destabilizing	0.330	Likely Benign	-5.46	Deleterious	0.435	Benign	0.920	Probably Damaging	1.61	Pathogenic	0.02	Affected			0.2316	0.2522		-1	-3	-4.6	-42.08
c.2444G>C	R815P 2D AIThe SynGAP1 missense variant R815P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default) predict a pathogenic impact. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Overall, the preponderance of evidence indicates that R815P is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250											-7.495	In-Between	0.858	Likely Pathogenic	Ambiguous										0.153	Likely Benign	-2.85	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.65	Benign	0.02	Affected			0.2113	0.4897		0	-2	2.9	-59.07
c.1049T>C	V350A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V350A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), premPS, PROVEAN, ESM1b, and FATHMM. Stability‑based methods FoldX, Rosetta, and Foldetta give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as unavailable. Overall, the predictions are split, with a slight edge toward pathogenicity from the consensus and high‑accuracy tools. Therefore, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-8.323	Likely Pathogenic	0.280	Likely Benign	Likely Benign	1.42	Ambiguous	0.0	1.97	Ambiguous	1.70	Ambiguous	2.07	Destabilizing	0.096	Likely Benign	-2.73	Deleterious	0.435	Benign	0.115	Benign	1.64	Pathogenic	0.55	Tolerated			0.3207	0.2967		0	0	-2.4	-28.05
c.2444G>T	R815L 2D AISynGAP1 missense variant R815L is listed in ClinVar (ID 2505666.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools indicates a pathogenic effect, which contrasts with the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1				-8.546	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.03	Affected	4.32	4	0.1817	0.5132		-2	-3	8.3	-43.03
c.1049T>A	V350E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign effect include REVEL and SIFT, whereas a majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, Foldetta, and Rosetta. Two tools give inconclusive results: FoldX (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for V350E. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-15.975	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.73	Ambiguous	0.2	2.61	Destabilizing	2.17	Destabilizing	1.93	Destabilizing	0.304	Likely Benign	-4.67	Deleterious	0.976	Probably Damaging	0.559	Possibly Damaging	1.61	Pathogenic	0.08	Tolerated			0.1078	0.1568		-2	-2	-7.7	29.98
c.2446T>A	S816T 2D AIThe SynGAP1 missense variant S816T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-3.957	Likely Benign	0.408	Ambiguous	Likely Benign										0.064	Likely Benign	-1.05	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.65	Benign	0.32	Tolerated			0.1573	0.5529		1	1	0.1	14.03
c.2446T>C	S816P 2D AIThe SynGAP1 missense variant S816P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus likewise indicates Likely Benign; Foldetta data are unavailable. Overall, the preponderance of evidence points to a benign effect for S816P, and this conclusion is not in conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-3.662	Likely Benign	0.510	Ambiguous	Likely Benign										0.160	Likely Benign	-0.26	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.66	Benign	0.45	Tolerated			0.2298	0.5102		1	-1	-0.8	10.04
c.2446T>G	S816A 2D AIThe SynGAP1 missense variant S816A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-4.543	Likely Benign	0.310	Likely Benign	Likely Benign										0.078	Likely Benign	-1.07	Neutral	0.953	Possibly Damaging	0.799	Possibly Damaging	2.67	Benign	0.59	Tolerated			0.5307	0.4532	Weaken	1	1	2.6	-16.00
c.2441C>G	A814G 2D AIThe SynGAP1 missense variant A814G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) score; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-3.659	Likely Benign	0.312	Likely Benign	Likely Benign										0.071	Likely Benign	-1.83	Neutral	0.896	Possibly Damaging	0.649	Possibly Damaging	2.60	Benign	0.05	Affected			0.2336	0.4504		1	0	-2.2	-14.03
c.2441C>A	A814D 2D AIThe SynGAP1 missense variant A814D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a tie and thus unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result. Overall, the balance of evidence from the consensus of standard predictors points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-5.641	Likely Benign	0.939	Likely Pathogenic	Ambiguous										0.158	Likely Benign	-2.56	Deleterious	0.968	Probably Damaging	0.810	Possibly Damaging	2.59	Benign	0.01	Affected			0.1740	0.2167		0	-2	-5.3	44.01
c.1051G>A	A351T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A351T missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta as inconclusive. Overall, the majority of evidence supports a benign impact for A351T, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000											-6.863	Likely Benign	0.077	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	0.80	Ambiguous	0.51	Ambiguous	0.49	Likely Benign	0.040	Likely Benign	-2.42	Neutral	0.524	Possibly Damaging	0.138	Benign	1.71	Pathogenic	0.06	Tolerated			0.1337	0.6713		1	0	-2.5	30.03
c.2435C>G	P812R 2D AIThe SynGAP1 P812R missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of standard predictors indicate a pathogenic impact, while the most accurate tools provide no definitive evidence. Thus, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.784	Likely Benign	0.799	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-2.70	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.77	Benign	0.01	Affected			0.1285	0.3525		0	-2	-2.9	59.07
c.104T>G	V35G 2D AIThe SynGAP1 missense variant V35G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus also predicts benign; Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because the variant is not currently catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.613573	Disordered	0.434838	Uncertain	0.360	0.851	0.375											-3.614	Likely Benign	0.109	Likely Benign	Likely Benign										0.143	Likely Benign	0.66	Neutral	0.693	Possibly Damaging	0.824	Possibly Damaging	4.41	Benign	0.00	Affected			0.1514	0.2618		-1	-3	-4.6	-42.08
c.2437C>A	L813M 2D AIThe SynGAP1 missense variant L813M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.893	Likely Benign	0.299	Likely Benign	Likely Benign										0.101	Likely Benign	-0.53	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.58	Benign	0.23	Tolerated			0.0814	0.3922		4	2	-1.9	18.03
c.2437C>G	L813V 2D AIThe SynGAP1 missense variant L813V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.809	Likely Benign	0.215	Likely Benign	Likely Benign										0.136	Likely Benign	-0.98	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	2.62	Benign	0.28	Tolerated			0.1704	0.3744		2	1	0.4	-14.03
c.2438T>A	L813Q 2D AIThe SynGAP1 missense variant L813Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence points to a benign impact for the variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-5.380	Likely Benign	0.660	Likely Pathogenic	Likely Benign										0.137	Likely Benign	-1.30	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.67	Benign	0.10	Tolerated			0.1122	0.1105		-2	-2	-7.3	14.97
c.2438T>C	L813P 2D AIThe SynGAP1 missense variant L813P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, and AlphaMissense‑Default remains uncertain. No Foldetta stability assessment is available, so it does not influence the overall interpretation. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-2.572	Likely Benign	0.554	Ambiguous	Likely Benign										0.122	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.58	Benign	0.21	Tolerated			0.3564	0.1458		-3	-3	-5.4	-16.04
c.2438T>G	L813R 2D AIThe SynGAP1 missense variant L813R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and Foldetta results are unavailable. Taken together, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.697	Likely Benign	0.786	Likely Pathogenic	Ambiguous										0.160	Likely Benign	-1.57	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.68	Benign	0.11	Tolerated			0.1261	0.0947		-3	-2	-8.3	43.03
c.2440G>A	A814T 2D AIThe SynGAP1 missense variant A814T is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome, while Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-3.600	Likely Benign	0.227	Likely Benign	Likely Benign										0.062	Likely Benign	-1.24	Neutral	0.103	Benign	0.047	Benign	2.64	Benign	0.09	Tolerated			0.1400	0.6655		1	0	-2.5	30.03
c.2440G>C	A814P 2D AIThe SynGAP1 missense variant A814P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for A814P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-5.247	Likely Benign	0.351	Ambiguous	Likely Benign										0.210	Likely Benign	-1.88	Neutral	0.984	Probably Damaging	0.855	Possibly Damaging	2.64	Benign	0.05	Affected			0.1845	0.4941		1	-1	-3.4	26.04
c.2440G>T	A814S 2D AIThe SynGAP1 missense variant A814S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-2.542	Likely Benign	0.147	Likely Benign	Likely Benign										0.067	Likely Benign	-1.22	Neutral	0.640	Possibly Damaging	0.386	Benign	2.63	Benign	0.06	Tolerated			0.2670	0.5366		1	1	-2.6	16.00
c.104T>C	V35A 2D AIThe SynGAP1 missense variant V35A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumVar and SIFT, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.613573	Disordered	0.434838	Uncertain	0.360	0.851	0.375											-3.552	Likely Benign	0.120	Likely Benign	Likely Benign										0.098	Likely Benign	-0.05	Neutral	0.267	Benign	0.481	Possibly Damaging	4.25	Benign	0.00	Affected			0.2340	0.2144		0	0	-2.4	-28.05
c.2447C>A	S816Y 2D AIThe SynGAP1 missense variant S816Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default, all of which classify the substitution as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, while Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-8.369	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-2.83	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.60	Benign	0.03	Affected			0.0668	0.4741		-3	-2	-0.5	76.10
c.2315T>G	F772C 2D AIThe SynGAP1 missense variant F772C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-4.498	Likely Benign	0.248	Likely Benign	Likely Benign										0.156	Likely Benign	-1.46	Neutral	0.979	Probably Damaging	0.985	Probably Damaging	4.14	Benign	0.10	Tolerated			0.2450	0.1419		-4	-2	-0.3	-44.04
c.231T>A	S77R 2D AIThe SynGAP1 missense variant S77R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the high‑accuracy tools) is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-2.823	Likely Benign	0.482	Ambiguous	Likely Benign										0.026	Likely Benign	-1.22	Neutral	0.198	Benign	0.015	Benign	4.09	Benign	0.00	Affected			0.0752	0.3247		0	-1	-3.7	69.11
c.231T>G	S77R 2D AIThe SynGAP1 missense variant S77R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the high‑accuracy tools) is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-2.823	Likely Benign	0.482	Ambiguous	Likely Benign										0.026	Likely Benign	-1.22	Neutral	0.198	Benign	0.015	Benign	4.09	Benign	0.00	Affected			0.0752	0.3247		0	-1	-3.7	69.11
c.2320G>A	A774T 2D AIThe SynGAP1 missense variant A774T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-3.238	Likely Benign	0.093	Likely Benign	Likely Benign										0.062	Likely Benign	-0.46	Neutral	0.037	Benign	0.063	Benign	4.20	Benign	0.39	Tolerated			0.1436	0.7578		1	0	-2.5	30.03
c.2320G>C	A774P 2D AIThe SynGAP1 missense variant A774P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-3.869	Likely Benign	0.192	Likely Benign	Likely Benign										0.116	Likely Benign	-0.94	Neutral	0.801	Possibly Damaging	0.481	Possibly Damaging	4.15	Benign	0.18	Tolerated			0.1902	0.5749		1	-1	-3.4	26.04
c.2320G>T	A774S 2D AIThe SynGAP1 missense variant A774S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-2.780	Likely Benign	0.079	Likely Benign	Likely Benign										0.090	Likely Benign	-0.09	Neutral	0.071	Benign	0.115	Benign	4.27	Benign	0.43	Tolerated			0.2711	0.6399		1	1	-2.6	16.00
c.1087T>G	Y363D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are none; all evaluated algorithms predict a deleterious impact. Pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-13.840	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.86	Destabilizing	0.2	3.03	Destabilizing	2.95	Destabilizing	1.73	Destabilizing	0.635	Likely Pathogenic	-8.94	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.4720	0.1853		-4	-3	-2.2	-48.09
c.2321C>A	A774D 2D AIThe SynGAP1 missense variant A774D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-4.455	Likely Benign	0.603	Likely Pathogenic	Likely Benign										0.123	Likely Benign	-0.46	Neutral	0.570	Possibly Damaging	0.386	Benign	4.21	Benign	0.06	Tolerated			0.1645	0.1793		0	-2	-5.3	44.01
c.2321C>G	A774G 2D AIThe SynGAP1 missense variant A774G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250											-3.129	Likely Benign	0.099	Likely Benign	Likely Benign										0.056	Likely Benign	-0.68	Neutral	0.135	Benign	0.152	Benign	4.16	Benign	0.22	Tolerated			0.2392	0.5436		1	0	-2.2	-14.03
c.1087T>C	Y363H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, while the majority of other in silico predictors (Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, Foldetta) indicate a pathogenic impact; FoldX and ESM1b are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for Y363H, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-7.003	In-Between	0.747	Likely Pathogenic	Likely Benign	1.75	Ambiguous	0.1	2.40	Destabilizing	2.08	Destabilizing	1.04	Destabilizing	0.419	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.56	Pathogenic	0.01	Affected			0.3267	0.2021		0	2	-1.9	-26.03
c.1087T>A	Y363N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363N is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify Y363N as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-12.121	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	2.06	Destabilizing	0.1	2.85	Destabilizing	2.46	Destabilizing	1.45	Destabilizing	0.477	Likely Benign	-8.04	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.55	Pathogenic	0.01	Affected			0.3117	0.2021		-2	-2	-2.2	-49.07
c.2323C>G	R775G 2D AIThe SynGAP1 missense variant R775G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R775G, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.895337	Binding	0.320	0.896	0.250											-4.186	Likely Benign	0.359	Ambiguous	Likely Benign										0.118	Likely Benign	-1.23	Neutral	0.933	Possibly Damaging	0.871	Possibly Damaging	4.12	Benign	0.07	Tolerated			0.3194	0.3761		-3	-2	4.1	-99.14
c.1086G>T	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact on protein stability. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.2319G>T	M773I 2D AIThe SynGAP1 missense variant M773I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-4.799	Likely Benign	0.567	Likely Pathogenic	Likely Benign										0.099	Likely Benign	-0.83	Neutral	0.038	Benign	0.284	Benign	4.31	Benign	0.22	Tolerated			0.1406	0.3011		2	1	2.6	-18.03
c.2319G>C	M773I 2D AIThe SynGAP1 missense variant M773I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-4.799	Likely Benign	0.567	Likely Pathogenic	Likely Benign										0.099	Likely Benign	-0.83	Neutral	0.038	Benign	0.284	Benign	4.31	Benign	0.22	Tolerated			0.1406	0.3011		2	1	2.6	-18.03
c.1090C>G	P364A 2D 3DClick to see structure in 3D Viewer AISynGAP1 P364A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Stability‑based methods (FoldX, Rosetta, premPS) give uncertain outcomes, and Foldetta is unavailable. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, does not provide a definitive result. Overall, the predictions are discordant; the majority of tools lean toward pathogenicity, but a substantial subset suggests benign. Based on the predictions, the variant is most likely pathogenic, and this does not contradict ClinVar status because there is no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-8.077	Likely Pathogenic	0.135	Likely Benign	Likely Benign	0.79	Ambiguous	0.0	0.69	Ambiguous	0.74	Ambiguous	0.60	Ambiguous	0.320	Likely Benign	-6.10	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.56	Pathogenic	0.06	Tolerated			0.3496	0.5186		1	-1	3.4	-26.04
c.1090C>A	P364T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P364T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Four tools (FoldX, Foldetta, premPS, ESM1b) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (five benign versus four pathogenic) lean toward a benign classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-7.951	In-Between	0.230	Likely Benign	Likely Benign	1.18	Ambiguous	0.6	0.47	Likely Benign	0.83	Ambiguous	0.53	Ambiguous	0.342	Likely Benign	-5.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.09	Tolerated			0.1660	0.5726		0	-1	0.9	3.99
c.2316C>G	F772L 2D AIThe SynGAP1 missense variant F772L has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability data are available, so it is treated as unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-1.751	Likely Benign	0.762	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-0.47	Neutral	0.508	Possibly Damaging	0.786	Possibly Damaging	4.31	Benign	1.00	Tolerated	3.64	6	0.1661	0.3033		0	2	1.0	-34.02
c.2317A>C	M773L 2D AIThe SynGAP1 missense variant M773L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-3.458	Likely Benign	0.114	Likely Benign	Likely Benign										0.211	Likely Benign	-0.75	Neutral	0.038	Benign	0.137	Benign	4.29	Benign	0.81	Tolerated			0.1517	0.3529		4	2	1.9	-18.03
c.108T>G	H36Q 2D AIThe SynGAP1 missense variant H36Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-3.642	Likely Benign	0.135	Likely Benign	Likely Benign										0.044	Likely Benign	-0.16	Neutral	0.182	Benign	0.046	Benign	4.34	Benign	0.00	Affected			0.2042	0.4572		3	0	-0.3	-9.01
c.108T>A	H36Q 2D AIThe SynGAP1 missense variant H36Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-3.642	Likely Benign	0.135	Likely Benign	Likely Benign										0.044	Likely Benign	-0.16	Neutral	0.182	Benign	0.046	Benign	4.34	Benign	0.00	Affected			0.2042	0.4572		3	0	-0.3	-9.01
c.2317A>G	M773V 2D AIThe SynGAP1 missense variant M773V has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence indicates that M773V is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-4.353	Likely Benign	0.126	Likely Benign	Likely Benign										0.234	Likely Benign	-0.70	Neutral	0.038	Benign	0.284	Benign	4.30	Benign	0.87	Tolerated			0.3145	0.3081		2	1	2.3	-32.06
c.2317A>T	M773L 2D AIThe SynGAP1 missense variant M773L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign impact, and this is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-3.458	Likely Benign	0.114	Likely Benign	Likely Benign										0.211	Likely Benign	-0.75	Neutral	0.038	Benign	0.137	Benign	4.29	Benign	0.81	Tolerated			0.1517	0.3529		4	2	1.9	-18.03
c.2318T>A	M773K 2D AIThe SynGAP1 missense variant M773K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-5.117	Likely Benign	0.641	Likely Pathogenic	Likely Benign										0.178	Likely Benign	-1.80	Neutral	0.106	Benign	0.471	Possibly Damaging	4.19	Benign	0.02	Affected			0.1646	0.0851		0	-1	-5.8	-3.02
c.1088A>T	Y363F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, seven tools predict benign while four predict pathogenic, with no evidence of pathogenicity from the most accurate methods. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-6.621	Likely Benign	0.114	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.42	Likely Benign	0.10	Likely Benign	0.58	Ambiguous	0.293	Likely Benign	-3.42	Deleterious	0.997	Probably Damaging	0.970	Probably Damaging	1.74	Pathogenic	0.18	Tolerated			0.2781	0.3583		7	3	4.1	-16.00
c.1088A>C	Y363S 2D AIThe SynGAP1 missense variant Y363S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized is classified as “Uncertain”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic effect for Y363S, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-11.578	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.6	3.92	Destabilizing	3.51	Destabilizing	1.45	Destabilizing	0.420	Likely Benign	-8.04	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.56	Pathogenic	0.01	Affected			0.5750	0.4208	Weaken	-3	-2	0.5	-76.10
c.2319G>A	M773I 2D AIThe SynGAP1 missense variant M773I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-4.799	Likely Benign	0.567	Likely Pathogenic	Likely Benign										0.099	Likely Benign	-0.83	Neutral	0.038	Benign	0.284	Benign	4.31	Benign	0.22	Tolerated			0.1406	0.3011		2	1	2.6	-18.03
c.1086G>C	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the consensus of all predictions, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.2324G>C	R775P 2D AIThe SynGAP1 missense variant R775P (ClinVar ID 2959355.0) is classified as Benign in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, consistent with the ClinVar designation, and there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.895337	Binding	0.320	0.896	0.250					Benign		1				-5.072	Likely Benign	0.452	Ambiguous	Likely Benign										0.168	Likely Benign	-0.79	Neutral	0.971	Probably Damaging	0.944	Probably Damaging	4.13	Benign	0.07	Tolerated	3.64	6	0.1891	0.4834		-2	0	2.9	-59.07
c.1085G>T	W362L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362L is not reported in ClinVar and is absent from gnomAD. All tools except premPS predict pathogenic, leaving no benign predictions. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. High‑accuracy methods corroborate this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-12.748	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.1	2.60	Destabilizing	2.38	Destabilizing	0.71	Ambiguous	0.523	Likely Pathogenic	-11.95	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.2701	0.2452		-2	-2	4.7	-73.05
c.2330T>G	L777R 2D AIThe SynGAP1 missense variant L777R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-6.084	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.227	Likely Benign	-2.20	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.97	Benign	0.00	Affected			0.1249	0.0846		-3	-2	-8.3	43.03
c.2332A>C	N778H 2D AIThe SynGAP1 missense variant N778H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-4.761	Likely Benign	0.172	Likely Benign	Likely Benign										0.100	Likely Benign	-1.62	Neutral	0.991	Probably Damaging	0.980	Probably Damaging	4.17	Benign	0.04	Affected			0.1400	0.7220		2	1	0.3	23.04
c.2332A>G	N778D 2D AIThe SynGAP1 missense variant N778D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-4.838	Likely Benign	0.446	Ambiguous	Likely Benign										0.093	Likely Benign	-0.86	Neutral	0.843	Possibly Damaging	0.893	Possibly Damaging	4.21	Benign	0.15	Tolerated			0.1896	0.4528		2	1	0.0	0.98
c.1082A>T	Q361L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8 benign vs 5 pathogenic) favor a benign effect, and this consensus does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-10.678	Likely Pathogenic	0.238	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.46	Likely Benign	0.29	Likely Benign	0.21	Likely Benign	0.406	Likely Benign	-3.95	Deleterious	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.06	Tolerated			0.0720	0.5213		-2	-2	7.3	-14.97
c.2332A>T	N778Y 2D AIThe SynGAP1 missense variant N778Y is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). AlphaMissense‑Default is uncertain, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support a benign interpretation: 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. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-5.723	Likely Benign	0.421	Ambiguous	Likely Benign										0.175	Likely Benign	-2.48	Neutral	0.991	Probably Damaging	0.980	Probably Damaging	4.16	Benign	0.02	Affected			0.0589	0.6139		-2	-2	2.2	49.07
c.2333A>C	N778T 2D AIThe SynGAP1 missense variant N778T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-3.820	Likely Benign	0.222	Likely Benign	Likely Benign										0.110	Likely Benign	-1.52	Neutral	0.925	Possibly Damaging	0.932	Probably Damaging	4.23	Benign	0.09	Tolerated			0.1441	0.7395		0	0	2.8	-13.00
c.1082A>G	Q361R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, SIFT, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus itself is benign; and Foldetta, which integrates FoldX‑MD (Uncertain) and Rosetta (Benign), yields a benign prediction. Overall, the consensus of available computational evidence indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-6.898	Likely Benign	0.289	Likely Benign	Likely Benign	-0.88	Ambiguous	0.0	-0.07	Likely Benign	-0.48	Likely Benign	-0.20	Likely Benign	0.296	Likely Benign	-0.56	Neutral	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.41	Tolerated			0.1321	0.2955		1	1	-1.0	28.06
c.1082A>C	Q361P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361P is listed in ClinVar as Pathogenic (ClinVar ID 3235087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the overwhelming agreement of these predictions, the variant is most likely pathogenic, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250					Likely Pathogenic		1				-13.280	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	3.12	Destabilizing	0.0	3.45	Destabilizing	3.29	Destabilizing	0.38	Likely Benign	0.482	Likely Benign	-3.03	Deleterious	0.996	Probably Damaging	0.979	Probably Damaging	1.63	Pathogenic	0.05	Affected	3.37	25	0.1986	0.5151		-1	0	1.9	-31.01
c.1081C>G	Q361E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Uncertain predictions come from Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta remains uncertain. Taken together, the majority of evidence supports a benign impact for Q361E, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-7.544	In-Between	0.289	Likely Benign	Likely Benign	0.29	Likely Benign	0.0	1.02	Ambiguous	0.66	Ambiguous	0.21	Likely Benign	0.153	Likely Benign	-0.89	Neutral	0.969	Probably Damaging	0.930	Probably Damaging	1.70	Pathogenic	0.26	Tolerated			0.1217	0.3018		2	2	0.0	0.98
c.2334C>G	N778K 2D AIThe SynGAP1 missense variant N778K has no ClinVar record and is not listed in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the preponderance of evidence points to a benign effect. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-6.768	Likely Benign	0.798	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-1.57	Neutral	0.925	Possibly Damaging	0.932	Probably Damaging	4.27	Benign	0.18	Tolerated	3.64	6	0.2037	0.5883		0	1	-0.4	14.07
c.2335A>C	S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2335A>G	S779G 2D AIThe SynGAP1 missense variant S779G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.304	Likely Benign	0.111	Likely Benign	Likely Benign										0.103	Likely Benign	0.38	Neutral	0.393	Benign	0.324	Benign	2.65	Benign	0.53	Tolerated			0.2894	0.5087		1	0	0.4	-30.03
c.1083G>C	Q361H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—FoldX, Rosetta, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, while the single high‑accuracy tool suggests benign. No ClinVar annotation exists to contradict these findings. Thus, based on the collective evidence, the variant is most likely pathogenic, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-7.269	In-Between	0.410	Ambiguous	Likely Benign	0.68	Ambiguous	0.1	0.52	Ambiguous	0.60	Ambiguous	0.32	Likely Benign	0.281	Likely Benign	-2.73	Deleterious	0.996	Probably Damaging	0.986	Probably Damaging	1.79	Pathogenic	0.04	Affected			0.1352	0.4151		3	0	0.3	9.01
c.1083G>T	Q361H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—FoldX, Rosetta, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. Overall, the majority of conventional predictors (five pathogenic vs. three benign) lean toward a pathogenic interpretation, while the single high‑accuracy tool suggests benign. No ClinVar entry exists, so there is no contradiction with clinical database status. Based on the collective evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-7.269	In-Between	0.410	Ambiguous	Likely Benign	0.68	Ambiguous	0.1	0.52	Ambiguous	0.60	Ambiguous	0.32	Likely Benign	0.281	Likely Benign	-2.73	Deleterious	0.996	Probably Damaging	0.986	Probably Damaging	1.79	Pathogenic	0.04	Affected			0.1352	0.4151		3	0	0.3	9.01
c.1085G>C	W362S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic, while premPS remains uncertain. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) also indicates pathogenic. No tool predicts a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-13.228	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	4.08	Destabilizing	0.0	4.55	Destabilizing	4.32	Destabilizing	0.95	Ambiguous	0.625	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.31	Pathogenic	0.00	Affected			0.5106	0.1215	Weaken	-2	-3	0.1	-99.14
c.2326G>C	G776R 2D AIThe SynGAP1 missense variant G776R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the Foldetta protein‑folding stability assessment is unavailable for this variant. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250											-6.209	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.28	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	4.22	Benign	0.01	Affected			0.0932	0.5115		-3	-2	-4.1	99.14
c.1084T>G	W362G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD, so no population frequency data are available. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the single uncertain call (premPS) does not alter the overall consensus. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Thus, based on the collective predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-14.242	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	4.22	Destabilizing	0.1	5.28	Destabilizing	4.75	Destabilizing	0.95	Ambiguous	0.707	Likely Pathogenic	-11.95	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.25	Pathogenic	0.00	Affected			0.4751	0.1281		-7	-2	0.5	-129.16
c.1084T>C	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R (ClinVar ID 41461.0) is listed 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 concur: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. 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	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125					Pathogenic		2				-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.2327G>C	G776A 2D AIThe SynGAP1 missense variant G776A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G776A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250											-5.275	Likely Benign	0.296	Likely Benign	Likely Benign										0.173	Likely Benign	-1.82	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	4.26	Benign	0.03	Affected			0.3648	0.4971		1	0	2.2	14.03
c.1084T>A	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic. Benign predictions are absent; all evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return pathogenic or likely pathogenic calls. High‑accuracy assessments corroborate 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) also reports pathogenic. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.2329C>G	L777V 2D AIThe SynGAP1 missense variant L777V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-5.693	Likely Benign	0.134	Likely Benign	Likely Benign										0.084	Likely Benign	-1.05	Neutral	0.843	Possibly Damaging	0.920	Probably Damaging	4.07	Benign	0.05	Affected			0.1651	0.3977		2	1	0.4	-14.03
c.2329C>T	L777F 2D AIThe SynGAP1 missense variant L777F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-4.499	Likely Benign	0.175	Likely Benign	Likely Benign										0.115	Likely Benign	-1.91	Neutral	0.968	Probably Damaging	0.966	Probably Damaging	3.98	Benign	0.01	Affected			0.0697	0.3576		2	0	-1.0	34.02
c.232C>A	R78S 2D AIThe SynGAP1 missense variant R78S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments are: AlphaMissense‑Optimized (Uncertain), SGM‑Consensus (Likely Benign), and Foldetta (no data available). Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-3.680	Likely Benign	0.792	Likely Pathogenic	Ambiguous										0.063	Likely Benign	-1.11	Neutral	0.385	Benign	0.015	Benign	3.86	Benign	0.00	Affected			0.3081	0.3274		0	-1	3.7	-69.11
c.232C>G	R78G 2D AIThe SynGAP1 R78G missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign status: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Taken together, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-3.972	Likely Benign	0.480	Ambiguous	Likely Benign										0.072	Likely Benign	-1.94	Neutral	0.385	Benign	0.028	Benign	3.83	Benign	0.00	Affected			0.3285	0.2986		-3	-2	4.1	-99.14
c.232C>T	R78C 2D AIThe SynGAP1 missense variant R78C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R78C, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-6.079	Likely Benign	0.467	Ambiguous	Likely Benign										0.114	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.194	Benign	3.80	Benign	0.00	Affected			0.3255	0.2804		-4	-3	7.0	-53.05
c.2330T>A	L777H 2D AIThe SynGAP1 missense variant L777H has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence—including the consensus of high‑accuracy tools—suggests that the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-6.719	Likely Benign	0.492	Ambiguous	Likely Benign										0.230	Likely Benign	-2.51	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	3.95	Benign	0.00	Affected			0.1052	0.0972		-2	-3	-7.0	23.98
c.2335A>T	S779C 2D AIThe SynGAP1 missense variant S779C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-6.375	Likely Benign	0.196	Likely Benign	Likely Benign										0.230	Likely Benign	-1.88	Neutral	0.992	Probably Damaging	0.905	Possibly Damaging	2.28	Pathogenic	0.05	Affected			0.1177	0.6350		0	-1	3.3	16.06
c.109T>A	S37T 2D AIThe SynGAP1 missense variant S37T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-3.854	Likely Benign	0.134	Likely Benign	Likely Benign										0.062	Likely Benign	-0.60	Neutral	0.140	Benign	0.481	Possibly Damaging	3.95	Benign	0.00	Affected			0.2093	0.5974		1	1	0.1	14.03
c.1097C>A	T366N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change T366N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate a benign or likely benign outcome. Only two tools—polyPhen‑2 HumDiv and FATHMM—suggest a pathogenic effect, while premPS remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as benign. Taken together, the majority of evidence supports a benign impact and is consistent with the absence of any ClinVar pathogenic annotation. Therefore, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-5.694	Likely Benign	0.176	Likely Benign	Likely Benign	0.06	Likely Benign	0.0	0.36	Likely Benign	0.21	Likely Benign	0.92	Ambiguous	0.038	Likely Benign	-1.72	Neutral	0.454	Possibly Damaging	0.038	Benign	1.72	Pathogenic	0.34	Tolerated			0.1595	0.4934		0	0	-2.8	13.00
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		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125					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	0.1274	0.1889		0	-1	-5.2	-12.05
c.2300T>G	I767S 2D AIThe SynGAP1 missense variant I767S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are not available. Taken together, the preponderance of evidence points to a benign classification for I767S, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-3.030	Likely Benign	0.388	Ambiguous	Likely Benign										0.126	Likely Benign	-0.64	Neutral	0.925	Possibly Damaging	0.329	Benign	4.13	Benign	0.25	Tolerated			0.3242	0.1782		-1	-2	-5.3	-26.08
c.2301C>G	I767M 2D AIThe SynGAP1 missense variant I767M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence supports a benign classification for I767M, and this conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-2.384	Likely Benign	0.084	Likely Benign	Likely Benign										0.089	Likely Benign	-0.60	Neutral	0.835	Possibly Damaging	0.486	Possibly Damaging	4.05	Benign	0.11	Tolerated			0.0788	0.3377		2	1	-2.6	18.03
c.1096A>T	T366S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T366S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and Foldetta 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. There is no conflict with ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.273	Likely Benign	0.085	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.92	Ambiguous	0.53	Ambiguous	0.27	Likely Benign	0.058	Likely Benign	0.00	Neutral	0.005	Benign	0.001	Benign	1.73	Pathogenic	0.78	Tolerated			0.3549	0.4878		1	1	-0.1	-14.03
c.2302G>C	D768H 2D AIThe SynGAP1 D768H missense variant is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of predictions (5 benign vs. 4 pathogenic) and the high‑accuracy benign call suggest the variant is most likely benign, with no ClinVar status to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-8.673	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign										0.160	Likely Benign	-1.85	Neutral	0.966	Probably Damaging	0.737	Possibly Damaging	4.03	Benign	0.12	Tolerated			0.1450	0.8136		1	-1	0.3	22.05
c.2303A>G	D768G 2D AIThe SynGAP1 D768G missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all predict benign, whereas AlphaMissense‑Default predicts pathogenic. The high‑accuracy AlphaMissense‑Optimized result is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, which would provide a protein‑folding stability assessment, has no available output for this variant. Overall, the preponderance of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-7.150	In-Between	0.697	Likely Pathogenic	Likely Benign										0.184	Likely Benign	0.03	Neutral	0.393	Benign	0.131	Benign	4.09	Benign	0.72	Tolerated			0.4130	0.7476		1	-1	3.1	-58.04
c.2303A>T	D768V 2D AIThe SynGAP1 D768V variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-9.528	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.164	Likely Benign	-2.62	Deleterious	0.611	Possibly Damaging	0.140	Benign	4.04	Benign	0.02	Affected			0.0802	0.8019		-2	-3	7.7	-15.96
c.1096A>G	T366A 2D AIThe SynGAP1 missense variant T366A is not reported in ClinVar and is absent from gnomAD. Consensus among most in silico predictors indicates a benign effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. Only FATHMM predicts a pathogenic outcome, while Foldetta, premPS, and Rosetta are inconclusive and are treated as unavailable evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and Foldetta provides no definitive stability change. Overall, the computational evidence overwhelmingly favors a benign classification, and this is consistent with the absence of any ClinVar assertion. Therefore, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.983	Likely Benign	0.082	Likely Benign	Likely Benign	0.21	Likely Benign	0.5	0.86	Ambiguous	0.54	Ambiguous	0.51	Ambiguous	0.046	Likely Benign	-0.94	Neutral	0.031	Benign	0.016	Benign	1.73	Pathogenic	0.45	Tolerated			0.4141	0.4785		1	0	2.5	-30.03
c.2304C>A	D768E 2D AIThe SynGAP1 missense variant D768E is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts a benign outcome. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the computational evidence strongly supports a benign effect for D768E, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-4.611	Likely Benign	0.380	Ambiguous	Likely Benign										0.065	Likely Benign	-1.23	Neutral	0.393	Benign	0.171	Benign	4.16	Benign	0.17	Tolerated			0.1368	0.7729		3	2	0.0	14.03
c.2304C>G	D768E 2D AIThe SynGAP1 missense variant D768E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence strongly suggests that D768E is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-4.611	Likely Benign	0.380	Ambiguous	Likely Benign										0.065	Likely Benign	-1.23	Neutral	0.393	Benign	0.171	Benign	4.16	Benign	0.17	Tolerated			0.1368	0.7729		3	2	0.0	14.03
c.1096A>C	T366P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T366P is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors leans toward a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign) all classify the substitution as tolerated. In contrast, polyPhen‑2 HumDiv, FATHMM, Rosetta, and the Foldetta stability analysis predict a damaging or pathogenic outcome. FoldX reports an uncertain effect and is therefore not considered evidence. High‑accuracy tools give mixed results: AlphaMissense‑Optimized and the SGM‑Consensus both indicate benign, whereas Foldetta predicts pathogenic. Overall, the majority of predictors (8 benign vs. 4 pathogenic) support a benign classification, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-6.483	Likely Benign	0.226	Likely Benign	Likely Benign	1.75	Ambiguous	0.5	3.10	Destabilizing	2.43	Destabilizing	0.47	Likely Benign	0.150	Likely Benign	-2.49	Neutral	0.627	Possibly Damaging	0.139	Benign	1.70	Pathogenic	0.24	Tolerated			0.2250	0.6251		0	-1	-0.9	-3.99
c.2300T>A	I767N 2D AIThe SynGAP1 missense variant I767N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-5.117	Likely Benign	0.541	Ambiguous	Likely Benign										0.122	Likely Benign	-0.16	Neutral	0.977	Probably Damaging	0.632	Possibly Damaging	4.04	Benign	0.06	Tolerated			0.1039	0.1012		-2	-3	-8.0	0.94
c.22A>T	I8F 2D AIThe SynGAP1 missense variant I8F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-3.000	Likely Benign	0.092	Likely Benign	Likely Benign										0.116	Likely Benign	-0.29	Neutral	0.000	Benign	0.000	Benign	4.02	Benign	0.00	Affected			0.0483	0.2871		1	0	-1.7	34.02
c.2296T>G	S766A 2D AIThe SynGAP1 missense variant S766A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250											-6.115	Likely Benign	0.186	Likely Benign	Likely Benign										0.055	Likely Benign	-0.98	Neutral	0.447	Benign	0.198	Benign	4.17	Benign	0.02	Affected			0.5059	0.5705	Strenghten	1	1	2.6	-16.00
c.1099C>G	L367V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L367V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign effect for L367V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-2.383	Likely Benign	0.066	Likely Benign	Likely Benign	1.48	Ambiguous	0.2	1.72	Ambiguous	1.60	Ambiguous	0.15	Likely Benign	0.040	Likely Benign	0.19	Neutral	0.410	Benign	0.104	Benign	1.67	Pathogenic	0.13	Tolerated			0.2321	0.3285		2	1	0.4	-14.03
c.2297C>G	S766C 2D AIThe SynGAP1 missense variant S766C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S766C, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250											-7.681	In-Between	0.326	Likely Benign	Likely Benign										0.192	Likely Benign	-2.02	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	4.07	Benign	0.00	Affected			0.1049	0.6110		0	-1	3.3	16.06
c.1099C>A	L367M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L367M variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and FATHMM. The remaining predictions are uncertain: Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also likely benign; Foldetta remains inconclusive. Overall, the majority of evidence supports a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-4.968	Likely Benign	0.111	Likely Benign	Likely Benign	0.22	Likely Benign	0.1	0.92	Ambiguous	0.57	Ambiguous	-0.04	Likely Benign	0.078	Likely Benign	0.12	Neutral	0.947	Possibly Damaging	0.360	Benign	1.63	Pathogenic	0.13	Tolerated			0.1402	0.3947		4	2	-1.9	18.03
c.2299A>C	I767L 2D AIThe SynGAP1 missense variant I767L is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-1.881	Likely Benign	0.112	Likely Benign	Likely Benign										0.159	Likely Benign	-0.73	Neutral	0.001	Benign	0.002	Benign	4.13	Benign	0.34	Tolerated			0.1020	0.4317		2	2	-0.7	0.00
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		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125					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	0.1418	0.4227		4	3	-0.3	-14.03
c.2299A>T	I767F 2D AIThe SynGAP1 missense variant I767F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-3.618	Likely Benign	0.162	Likely Benign	Likely Benign										0.213	Likely Benign	-1.37	Neutral	0.003	Benign	0.002	Benign	4.04	Benign	0.06	Tolerated			0.0643	0.3567		1	0	-1.7	34.02
c.229A>C	S77R 2D AIThe SynGAP1 missense variant S77R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign interpretation: 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 collective evidence points to a benign effect for S77R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-2.823	Likely Benign	0.482	Ambiguous	Likely Benign										0.011	Likely Benign	-1.22	Neutral	0.198	Benign	0.015	Benign	4.09	Benign	0.00	Affected			0.0752	0.3247		0	-1	-3.7	69.11
c.229A>T	S77C 2D AIThe SynGAP1 missense variant S77C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-5.549	Likely Benign	0.061	Likely Benign	Likely Benign										0.022	Likely Benign	-0.94	Neutral	0.953	Possibly Damaging	0.129	Benign	4.04	Benign	0.00	Affected			0.0954	0.5144		0	-1	3.3	16.06
c.1097C>G	T366S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T366S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and Foldetta 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. There is no conflict with ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.273	Likely Benign	0.085	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.92	Ambiguous	0.53	Ambiguous	0.27	Likely Benign	0.051	Likely Benign	0.00	Neutral	0.005	Benign	0.001	Benign	1.73	Pathogenic	0.78	Tolerated			0.3549	0.4878		1	1	-0.1	-14.03
c.22A>C	I8L 2D AIThe SynGAP1 missense variant I8L is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote from the four high‑accuracy tools) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the I8L variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-1.752	Likely Benign	0.083	Likely Benign	Likely Benign										0.124	Likely Benign	0.08	Neutral	0.002	Benign	0.000	Benign	4.20	Benign	0.00	Affected			0.0707	0.3776		2	2	-0.7	0.00
c.22A>G	I8V 2D AIThe SynGAP1 missense variant I8V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-2.723	Likely Benign	0.081	Likely Benign	Likely Benign										0.122	Likely Benign	-0.01	Neutral	0.005	Benign	0.001	Benign	4.22	Benign	0.00	Affected			0.1031	0.3470		4	3	-0.3	-14.03
c.2305C>G	L769V 2D AIThe SynGAP1 missense variant L769V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-4.585	Likely Benign	0.106	Likely Benign	Likely Benign										0.075	Likely Benign	-0.41	Neutral	0.625	Possibly Damaging	0.249	Benign	4.04	Benign	0.25	Tolerated			0.1364	0.2558		2	1	0.4	-14.03
c.1094T>G	V365G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-13.020	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	4.18	Destabilizing	0.2	4.83	Destabilizing	4.51	Destabilizing	2.18	Destabilizing	0.576	Likely Pathogenic	-5.88	Deleterious	0.688	Possibly Damaging	0.989	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1835	0.2717		-1	-3	-4.6	-42.08
c.1094T>C	V365A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and polyPhen‑2 HumVar, whereas the remaining tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic effect. High‑accuracy assessments are consistent with a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a pathogenic effect. Taken together, the majority of evidence supports a pathogenic classification for V365A, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-8.954	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	2.61	Destabilizing	0.1	2.62	Destabilizing	2.62	Destabilizing	2.10	Destabilizing	0.297	Likely Benign	-3.18	Deleterious	0.622	Possibly Damaging	0.235	Benign	1.67	Pathogenic	0.01	Affected			0.2682	0.2962		0	0	-2.4	-28.05
c.2310G>C	Q770H 2D AIThe SynGAP1 missense variant Q770H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for Q770H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-4.241	Likely Benign	0.270	Likely Benign	Likely Benign										0.093	Likely Benign	-1.27	Neutral	0.962	Probably Damaging	0.515	Possibly Damaging	4.11	Benign	0.01	Affected			0.1579	0.4344		3	0	0.3	9.01
c.2310G>T	Q770H 2D AIThe SynGAP1 missense variant Q770H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-4.241	Likely Benign	0.270	Likely Benign	Likely Benign										0.093	Likely Benign	-1.27	Neutral	0.962	Probably Damaging	0.515	Possibly Damaging	4.11	Benign	0.01	Affected			0.1579	0.4344		3	0	0.3	9.01
c.2311T>A	S771T 2D AIThe SynGAP1 missense variant S771T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign impact. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-4.765	Likely Benign	0.112	Likely Benign	Likely Benign										0.060	Likely Benign	-1.38	Neutral	0.649	Possibly Damaging	0.433	Benign	4.07	Benign	0.23	Tolerated			0.1497	0.6310		1	1	0.1	14.03
c.2311T>C	S771P 2D AIThe SynGAP1 missense variant S771P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-5.045	Likely Benign	0.112	Likely Benign	Likely Benign										0.180	Likely Benign	-1.32	Neutral	0.901	Possibly Damaging	0.692	Possibly Damaging	4.03	Benign	0.19	Tolerated			0.2194	0.5515		1	-1	-0.8	10.04
c.2311T>G	S771A 2D AIThe SynGAP1 missense variant S771A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-4.337	Likely Benign	0.107	Likely Benign	Likely Benign										0.067	Likely Benign	-1.09	Neutral	0.025	Benign	0.014	Benign	4.09	Benign	0.62	Tolerated			0.5201	0.4745	Weaken	1	1	2.6	-16.00
c.2312C>A	S771Y 2D AIThe SynGAP1 missense variant S771Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-7.041	In-Between	0.397	Ambiguous	Likely Benign										0.176	Likely Benign	-2.13	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	4.02	Benign	0.05	Affected			0.0707	0.5155		-3	-2	-0.5	76.10
c.2312C>G	S771C 2D AIThe SynGAP1 missense variant S771C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-8.014	Likely Pathogenic	0.167	Likely Benign	Likely Benign										0.177	Likely Benign	-1.99	Neutral	0.990	Probably Damaging	0.917	Probably Damaging	4.01	Benign	0.07	Tolerated			0.1022	0.5899		0	-1	3.3	16.06
c.2312C>T	S771F 2D AIThe SynGAP1 missense variant S771F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-7.988	In-Between	0.525	Ambiguous	Likely Benign										0.189	Likely Benign	-2.29	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	4.02	Benign	0.04	Affected			0.0624	0.5428		-3	-2	3.6	60.10
c.2314T>A	F772I 2D AIThe SynGAP1 missense variant F772I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-2.925	Likely Benign	0.255	Likely Benign	Likely Benign										0.142	Likely Benign	-0.38	Neutral	0.845	Possibly Damaging	0.899	Possibly Damaging	4.24	Benign	0.41	Tolerated			0.1544	0.2051		1	0	1.7	-34.02
c.1091C>G	P364R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P364R missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; Foldetta’s stability analysis is uncertain. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-12.652	Likely Pathogenic	0.715	Likely Pathogenic	Likely Benign	0.95	Ambiguous	0.7	0.88	Ambiguous	0.92	Ambiguous	0.73	Ambiguous	0.416	Likely Benign	-6.76	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.57	Pathogenic	0.12	Tolerated			0.1520	0.3977		0	-2	-2.9	59.07
c.2314T>G	F772V 2D AIThe SynGAP1 missense variant F772V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are not available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-2.886	Likely Benign	0.191	Likely Benign	Likely Benign										0.161	Likely Benign	-0.43	Neutral	0.845	Possibly Damaging	0.899	Possibly Damaging	4.27	Benign	0.37	Tolerated			0.1687	0.2419		-1	-1	1.4	-48.04
c.2315T>A	F772Y 2D AIThe SynGAP1 missense variant F772Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-2.657	Likely Benign	0.117	Likely Benign	Likely Benign										0.114	Likely Benign	-0.54	Neutral	0.705	Possibly Damaging	0.786	Possibly Damaging	4.17	Benign	0.35	Tolerated			0.1058	0.1892		7	3	-4.1	16.00
c.230G>T	S77I 2D AIThe SynGAP1 missense variant S77I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-3.918	Likely Benign	0.140	Likely Benign	Likely Benign										0.038	Likely Benign	-1.41	Neutral	0.604	Possibly Damaging	0.029	Benign	4.07	Benign	0.00	Affected			0.0758	0.5165		-1	-2	5.3	26.08
c.1093G>C	V365L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365L is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess sequence conservation and functional impact uniformly classify the substitution as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity; only FoldX and Rosetta report uncertain stability changes, which are treated as unavailable evidence. 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, which integrates FoldX‑MD and Rosetta outputs, reports a benign effect on protein folding stability. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-6.141	Likely Benign	0.265	Likely Benign	Likely Benign	-0.72	Ambiguous	0.2	0.74	Ambiguous	0.01	Likely Benign	0.35	Likely Benign	0.065	Likely Benign	-1.71	Neutral	0.005	Benign	0.003	Benign	2.50	Benign	0.25	Tolerated	3.38	21	0.0852	0.5309		1	2	-0.4	14.03
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		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250					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			0.0554	0.2881		2	0	-1.0	34.02
c.2306T>A	L769H 2D AIThe SynGAP1 missense variant L769H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which classify the variant as benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, all of which report the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.038	Likely Benign	0.422	Ambiguous	Likely Benign										0.235	Likely Benign	-1.96	Neutral	0.977	Probably Damaging	0.721	Possibly Damaging	3.90	Benign	0.00	Affected			0.1016	0.0828		-2	-3	-7.0	23.98
c.1094T>A	V365E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365E is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts pathogenic. With all available evidence pointing to a damaging effect and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-16.263	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.99	Destabilizing	0.3	3.81	Destabilizing	3.90	Destabilizing	2.20	Destabilizing	0.613	Likely Pathogenic	-5.02	Deleterious	0.989	Probably Damaging	0.688	Possibly Damaging	1.66	Pathogenic	0.00	Affected			0.0849	0.2083		-2	-2	-7.7	29.98
c.2306T>C	L769P 2D AIThe SynGAP1 missense variant L769P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.261	Likely Benign	0.338	Likely Benign	Likely Benign										0.200	Likely Benign	-1.75	Neutral	0.925	Possibly Damaging	0.427	Benign	3.90	Benign	0.00	Affected			0.3573	0.1323		-3	-3	-5.4	-16.04
c.2306T>G	L769R 2D AIThe SynGAP1 missense variant L769R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.245	Likely Benign	0.493	Ambiguous	Likely Benign										0.206	Likely Benign	-1.66	Neutral	0.003	Benign	0.006	Benign	3.91	Benign	0.00	Affected			0.1286	0.0702		-3	-2	-8.3	43.03
c.2308C>A	Q770K 2D AIThe SynGAP1 missense variant Q770K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-4.768	Likely Benign	0.367	Ambiguous	Likely Benign										0.106	Likely Benign	-0.72	Neutral	0.002	Benign	0.003	Benign	4.20	Benign	0.14	Tolerated			0.1984	0.4737		1	1	-0.4	0.04
c.2308C>G	Q770E 2D AIThe SynGAP1 missense variant Q770E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-4.782	Likely Benign	0.201	Likely Benign	Likely Benign										0.109	Likely Benign	-0.82	Neutral	0.002	Benign	0.003	Benign	4.19	Benign	0.04	Affected			0.1465	0.2833		2	2	0.0	0.98
c.2309A>C	Q770P 2D AIThe SynGAP1 missense variant Q770P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q770P, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-3.948	Likely Benign	0.087	Likely Benign	Likely Benign										0.178	Likely Benign	-1.00	Neutral	0.748	Possibly Damaging	0.170	Benign	4.10	Benign	0.02	Affected			0.2435	0.5717		0	-1	1.9	-31.01
c.2309A>G	Q770R 2D AIThe SynGAP1 missense variant Q770R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the collective evidence strongly suggests that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-3.873	Likely Benign	0.344	Ambiguous	Likely Benign										0.175	Likely Benign	-1.38	Neutral	0.194	Benign	0.071	Benign	4.14	Benign	0.07	Tolerated			0.1610	0.2580		1	1	-1.0	28.06
c.2309A>T	Q770L 2D AIThe SynGAP1 missense variant Q770L is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q770L, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-5.524	Likely Benign	0.521	Ambiguous	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.095	Benign	0.030	Benign	4.14	Benign	0.01	Affected			0.0776	0.6230		-2	-2	7.3	-14.97
c.230G>A	S77N 2D AIThe SynGAP1 missense variant S77N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-4.597	Likely Benign	0.101	Likely Benign	Likely Benign										0.063	Likely Benign	-0.78	Neutral	0.000	Benign	0.000	Benign	4.09	Benign	0.00	Affected			0.1088	0.3774		1	1	-2.7	27.03
c.230G>C	S77T 2D AIThe SynGAP1 missense variant S77T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375											-4.204	Likely Benign	0.068	Likely Benign	Likely Benign										0.058	Likely Benign	-0.03	Neutral	0.092	Benign	0.007	Benign	4.19	Benign	0.00	Affected			0.1180	0.5003		1	1	0.1	14.03
c.2315T>C	F772S 2D AIThe SynGAP1 missense variant F772S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus likewise indicates Likely Benign; Foldetta data are not available. Overall, the preponderance of evidence points to a benign effect for F772S, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-2.722	Likely Benign	0.442	Ambiguous	Likely Benign										0.138	Likely Benign	-0.26	Neutral	0.845	Possibly Damaging	0.899	Possibly Damaging	4.21	Benign	0.56	Tolerated			0.4134	0.0558		-3	-2	-3.6	-60.10
c.2359C>G	P787A 2D AIThe SynGAP1 P787A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM) predict a pathogenic impact. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic versus three benign predictions, with the SGM Consensus supporting pathogenicity—suggests that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-4.542	Likely Benign	0.451	Ambiguous	Likely Benign										0.242	Likely Benign	-4.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.48	Pathogenic	0.02	Affected			0.3425	0.4444		1	-1	3.4	-26.04
c.2363C>G	S788C 2D AIThe SynGAP1 missense variant S788C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, while five tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM) predict a pathogenic outcome. Two tools (ESM1b and AlphaMissense‑Default) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-7.935	In-Between	0.472	Ambiguous	Likely Benign										0.269	Likely Benign	-3.90	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.1393	0.6073		0	-1	3.3	16.06
c.2363C>T	S788F 2D AIThe SynGAP1 missense variant S788F is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; Foldetta stability analysis is unavailable. Overall, the preponderance of predictions points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-7.870	In-Between	0.749	Likely Pathogenic	Likely Benign										0.275	Likely Benign	-4.73	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0781	0.5824		-3	-2	3.6	60.10
c.2365C>A	P789T 2D AIThe SynGAP1 P789T missense variant has no ClinVar entry and is not present in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that P789T is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-5.242	Likely Benign	0.356	Ambiguous	Likely Benign										0.224	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.1371	0.3837		0	-1	0.9	3.99
c.2365C>G	P789A 2D AIThe SynGAP1 P789A missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie (2 benign, 2 pathogenic) and is therefore inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus remains inconclusive and Foldetta data are unavailable. Overall, the majority of tools (five out of nine) predict pathogenicity, but the presence of four benign predictions and the inconclusive high‑accuracy results suggest uncertainty. The variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-4.777	Likely Benign	0.235	Likely Benign	Likely Benign										0.258	Likely Benign	-4.92	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.3120	0.3052		1	-1	3.4	-26.04
c.2365C>T	P789S 2D AIThe SynGAP1 P789S variant has no ClinVar entry (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify it as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, with five tools supporting a deleterious effect versus three supporting benignity. This prediction does not contradict ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-4.793	Likely Benign	0.409	Ambiguous	Likely Benign										0.221	Likely Benign	-4.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.19	Pathogenic	0.00	Affected			0.3100	0.3436		1	-1	0.8	-10.04
c.2366C>A	P789Q 2D AIThe SynGAP1 P789Q missense change is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-5.191	Likely Benign	0.465	Ambiguous	Likely Benign										0.235	Likely Benign	-4.53	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1284	0.3215		0	-1	-1.9	31.01
c.2366C>G	P789R 2D AIThe SynGAP1 missense variant P789R is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-2.503	Likely Benign	0.668	Likely Pathogenic	Likely Benign										0.354	Likely Benign	-5.04	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1353	0.2129		0	-2	-2.9	59.07
c.2366C>T	P789L 2D AIThe SynGAP1 P789L missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence (five pathogenic vs. three benign predictions, with the SGM Consensus supporting pathogenicity) indicates that P789L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-4.623	Likely Benign	0.457	Ambiguous	Likely Benign										0.303	Likely Benign	-5.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1958	0.4866		-3	-3	5.4	16.04
c.1073T>A	F358Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F358Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a Likely Benign result (3 benign vs. 1 pathogenic), and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. premPS is uncertain and is treated as unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-6.458	Likely Benign	0.606	Likely Pathogenic	Likely Benign	0.42	Likely Benign	0.1	0.21	Likely Benign	0.32	Likely Benign	0.84	Ambiguous	0.231	Likely Benign	-2.17	Neutral	0.993	Probably Damaging	0.952	Probably Damaging	4.05	Benign	0.36	Tolerated			0.1467	0.2697		7	3	-4.1	16.00
c.2368A>G	T790A 2D AIThe SynGAP1 T790A missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, while the SGM Consensus remains inconclusive and Foldetta data are unavailable. Overall, the majority of standard predictors indicate pathogenicity, but the single high‑accuracy tool that is available suggests a benign effect, and no high‑accuracy tool provides a definitive pathogenic verdict. Consequently, the variant is most likely pathogenic according to the bulk of predictions, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-4.337	Likely Benign	0.096	Likely Benign	Likely Benign										0.167	Likely Benign	-2.64	Deleterious	0.992	Probably Damaging	0.989	Probably Damaging	2.35	Pathogenic	0.02	Affected			0.4157	0.4207		1	0	2.5	-30.03
c.2368A>T	T790S 2D AIThe SynGAP1 missense variant T790S is not reported in ClinVar and is absent from 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 further support a benign classification: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for T790S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-3.914	Likely Benign	0.123	Likely Benign	Likely Benign										0.125	Likely Benign	-1.83	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.39	Pathogenic	0.33	Tolerated	3.64	6	0.3416	0.4449		1	1	-0.1	-14.03
c.1072T>G	F358V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F358V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F358V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-9.021	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	1.42	Ambiguous	0.2	1.68	Ambiguous	1.55	Ambiguous	0.93	Ambiguous	0.408	Likely Benign	-5.32	Deleterious	0.993	Probably Damaging	0.968	Probably Damaging	4.09	Benign	0.18	Tolerated			0.2222	0.2978		-1	-1	1.4	-48.04
c.2363C>A	S788Y 2D AIThe SynGAP1 missense variant S788Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, AlphaMissense‑Optimized is uncertain (treated as unavailable), and Foldetta results are not provided. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-8.745	Likely Pathogenic	0.795	Likely Pathogenic	Ambiguous										0.251	Likely Benign	-4.56	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0844	0.5551		-3	-2	-0.5	76.10
c.2362T>G	S788A 2D AIThe SynGAP1 missense variant S788A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for S788A. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-5.381	Likely Benign	0.255	Likely Benign	Likely Benign										0.088	Likely Benign	-2.24	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	1.59	Pathogenic	0.02	Affected			0.5079	0.5041	Strenghten	1	1	2.6	-16.00
c.1075A>G	T359A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T359A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-2.948	Likely Benign	0.062	Likely Benign	Likely Benign	0.09	Likely Benign	0.0	0.73	Ambiguous	0.41	Likely Benign	0.45	Likely Benign	0.103	Likely Benign	-0.73	Neutral	0.000	Benign	0.001	Benign	1.79	Pathogenic	0.34	Tolerated			0.4215	0.4713		1	0	2.5	-30.03
c.1075A>C	T359P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T359P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-6.884	Likely Benign	0.319	Likely Benign	Likely Benign	0.97	Ambiguous	0.1	1.27	Ambiguous	1.12	Ambiguous	0.68	Ambiguous	0.248	Likely Benign	-2.36	Neutral	0.627	Possibly Damaging	0.091	Benign	1.78	Pathogenic	0.14	Tolerated			0.2352	0.5611		0	-1	-0.9	-3.99
c.235A>C	N79H 2D AIThe SynGAP1 missense variant N79H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-2.090	Likely Benign	0.110	Likely Benign	Likely Benign										0.045	Likely Benign	-0.72	Neutral	0.939	Possibly Damaging	0.114	Benign	4.16	Benign	0.00	Affected			0.1247	0.4718		2	1	0.3	23.04
c.1074C>G	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the majority of reliable tools predict a pathogenic impact for F358L. This conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.235A>G	N79D 2D AIThe SynGAP1 missense variant N79D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-3.746	Likely Benign	0.281	Likely Benign	Likely Benign										0.021	Likely Benign	-0.92	Neutral	0.371	Benign	0.018	Benign	4.19	Benign	0.00	Affected			0.1893	0.2535		2	1	0.0	0.98
c.235A>T	N79Y 2D AIThe SynGAP1 missense variant N79Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-2.844	Likely Benign	0.250	Likely Benign	Likely Benign										0.039	Likely Benign	-1.35	Neutral	0.939	Possibly Damaging	0.114	Benign	4.13	Benign	0.00	Affected			0.0510	0.4389		-2	-2	2.2	49.07
c.2360C>A	P787H 2D AIThe SynGAP1 missense variant P787H has no ClinVar entry and is not listed in gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic” (3 pathogenic votes versus 1 benign). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions lean toward pathogenicity, but this is contradicted by the benign call from AlphaMissense‑Optimized. Because ClinVar has no reported status, there is no conflict with existing clinical annotations. Thus, the variant is most likely pathogenic based on the prevailing computational evidence, though one high‑accuracy tool suggests a benign effect. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-5.819	Likely Benign	0.691	Likely Pathogenic	Likely Benign										0.308	Likely Benign	-4.96	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.1790	0.4061		0	-2	-1.6	40.02
c.1074C>A	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.2360C>G	P787R 2D AIThe SynGAP1 missense variant P787R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, whereas the single high‑accuracy tool indicates benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-5.013	Likely Benign	0.784	Likely Pathogenic	Likely Benign										0.268	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.50	Benign	0.03	Affected			0.1373	0.2741		0	-2	-2.9	59.07
c.2360C>T	P787L 2D AIThe SynGAP1 missense variant P787L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) lean toward pathogenicity, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-3.924	Likely Benign	0.747	Likely Pathogenic	Likely Benign										0.256	Likely Benign	-5.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.45	Pathogenic	0.01	Affected			0.2254	0.6034		-3	-3	5.4	16.04
c.1073T>G	F358C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F358C is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls arise from Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is inconclusive, Foldetta is inconclusive, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenic. Because the majority of available predictions favor a damaging effect, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.966	In-Between	0.927	Likely Pathogenic	Ambiguous	1.68	Ambiguous	0.1	2.19	Destabilizing	1.94	Ambiguous	1.18	Destabilizing	0.460	Likely Benign	-6.36	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	4.02	Benign	0.06	Tolerated			0.2364	0.1800		-4	-2	-0.3	-44.04
c.1073T>C	F358S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358S variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of algorithms predict a pathogenic outcome: FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Rosetta’s assessment is uncertain and is not taken as evidence. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of pathogenic predictions and the agreement of the high‑accuracy tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-9.316	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.32	Destabilizing	0.2	1.97	Ambiguous	2.15	Destabilizing	1.14	Destabilizing	0.493	Likely Benign	-6.48	Deleterious	0.998	Probably Damaging	0.986	Probably Damaging	4.07	Benign	0.20	Tolerated			0.3891	0.1333		-3	-2	-3.6	-60.10
c.1072T>C	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.290	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.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	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875					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	0.3416	0.4449		1	1	-0.1	-14.03
c.2369C>T	T790I 2D AIThe SynGAP1 missense variant T790I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-3.556	Likely Benign	0.482	Ambiguous	Likely Benign										0.190	Likely Benign	-3.08	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.28	Pathogenic	0.01	Affected			0.0987	0.5431		0	-1	5.2	12.05
c.2375A>G	E792G 2D AIThe SynGAP1 E792G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic vote). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta results are unavailable. Overall, the consensus of available predictions indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.925	Likely Benign	0.353	Ambiguous	Likely Benign										0.037	Likely Benign	-3.77	Deleterious	0.000	Benign	0.000	Benign	3.88	Benign	0.01	Affected			0.3145	0.6036		0	-2	3.1	-72.06
c.2375A>T	E792V 2D AIThe SynGAP1 E792V missense change is not listed in ClinVar and has no allele record in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-4.643	Likely Benign	0.640	Likely Pathogenic	Likely Benign										0.072	Likely Benign	-3.85	Deleterious	0.000	Benign	0.001	Benign	3.83	Benign	0.00	Affected			0.0987	0.7772		-2	-2	7.7	-29.98
c.2376A>C	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2376A>T	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2377A>C	K793Q 2D AIThe SynGAP1 missense variant K793Q is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta results are unavailable, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-2.838	Likely Benign	0.256	Likely Benign	Likely Benign										0.032	Likely Benign	-0.83	Neutral	0.174	Benign	0.099	Benign	4.13	Benign	0.06	Tolerated			0.5276	0.1540	Weaken	1	1	0.4	-0.04
c.1070A>T	H357L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv, while polyPhen‑2 HumVar and ESM1b are benign or uncertain, respectively. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (3 benign vs 1 pathogenic), and Foldetta also predicts benign. No predictions are missing or inconclusive. Overall, the variant is most likely benign based on the majority of computational evidence, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.281	In-Between	0.140	Likely Benign	Likely Benign	-0.18	Likely Benign	0.1	0.14	Likely Benign	-0.02	Likely Benign	0.10	Likely Benign	0.203	Likely Benign	-3.39	Deleterious	0.704	Possibly Damaging	0.169	Benign	4.20	Benign	0.25	Tolerated			0.1084	0.5971		-2	-3	7.0	-23.98
c.2378A>C	K793T 2D AIThe SynGAP1 missense variant K793T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only SIFT predicts a pathogenic outcome, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for K793T, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-3.861	Likely Benign	0.393	Ambiguous	Likely Benign										0.066	Likely Benign	-1.47	Neutral	0.174	Benign	0.123	Benign	4.12	Benign	0.03	Affected			0.2756	0.3473		0	-1	3.2	-27.07
c.2378A>G	K793R 2D AIThe SynGAP1 missense variant K793R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess sequence conservation and functional impact all converge on a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool in the dataset indicates pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” while Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-2.789	Likely Benign	0.113	Likely Benign	Likely Benign										0.026	Likely Benign	-0.29	Neutral	0.001	Benign	0.003	Benign	4.18	Benign	0.22	Tolerated			0.5270	0.1657	Weaken	3	2	-0.6	28.01
c.2378A>T	K793M 2D AIThe SynGAP1 K793M missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the balance of evidence, including the two high‑accuracy tools, points to a benign effect for K793M. This conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-4.762	Likely Benign	0.570	Likely Pathogenic	Likely Benign										0.073	Likely Benign	-1.49	Neutral	0.820	Possibly Damaging	0.601	Possibly Damaging	4.06	Benign	0.01	Affected			0.1674	0.4020		0	-1	5.8	3.02
c.1070A>G	H357R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. Two tools remain uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority; and Foldetta also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-9.212	Likely Pathogenic	0.348	Ambiguous	Likely Benign	-0.10	Likely Benign	0.3	1.07	Ambiguous	0.49	Likely Benign	0.32	Likely Benign	0.107	Likely Benign	-1.03	Neutral	0.495	Possibly Damaging	0.095	Benign	4.22	Benign	0.59	Tolerated			0.2147	0.2818		2	0	-1.3	19.05
c.2379G>T	K793N 2D AIThe SynGAP1 missense variant K793N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-5.162	Likely Benign	0.632	Likely Pathogenic	Likely Benign										0.040	Likely Benign	1.18	Neutral	0.174	Benign	0.135	Benign	4.13	Benign	0.47	Tolerated	4.07	3	0.4429	0.1976		0	1	0.4	-14.07
c.1070A>C	H357P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: Foldetta (protein‑folding stability) and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.953	In-Between	0.267	Likely Benign	Likely Benign	0.17	Likely Benign	0.9	3.52	Destabilizing	1.85	Ambiguous	-0.06	Likely Benign	0.197	Likely Benign	-2.70	Deleterious	0.936	Possibly Damaging	0.469	Possibly Damaging	4.18	Benign	0.17	Tolerated			0.2433	0.4468		0	-2	1.6	-40.02
c.1071C>A	H357Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H357Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. Based on the uniform predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-4.370	Likely Benign	0.163	Likely Benign	Likely Benign	0.06	Likely Benign	0.2	-0.03	Likely Benign	0.02	Likely Benign	-0.35	Likely Benign	0.025	Likely Benign	1.42	Neutral	0.013	Benign	0.007	Benign	4.49	Benign	1.00	Tolerated			0.1716	0.3850		3	0	-0.3	-9.01
c.2374G>C	E792Q 2D AIThe SynGAP1 missense variant E792Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” verdict, reflecting the majority of benign calls. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E792Q is most likely benign, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.782	Likely Benign	0.411	Ambiguous	Likely Benign										0.052	Likely Benign	-1.60	Neutral	0.077	Benign	0.049	Benign	3.89	Benign	0.02	Affected			0.1469	0.7401		2	2	0.0	-0.98
c.236A>C	N79T 2D AIThe SynGAP1 missense variant N79T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-3.752	Likely Benign	0.102	Likely Benign	Likely Benign										0.022	Likely Benign	-0.61	Neutral	0.371	Benign	0.018	Benign	4.21	Benign	0.00	Affected			0.1133	0.4890		0	0	2.8	-13.00
c.1072T>A	F358I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F358I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports an uncertain impact. Overall, the preponderance of evidence points to a pathogenic effect for F358I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-10.636	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.2	1.66	Ambiguous	1.30	Ambiguous	0.95	Ambiguous	0.393	Likely Benign	-4.45	Deleterious	0.993	Probably Damaging	0.977	Probably Damaging	4.07	Benign	0.13	Tolerated			0.2331	0.2821		1	0	1.7	-34.02
c.236A>G	N79S 2D AIThe SynGAP1 missense variant N79S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-2.311	Likely Benign	0.079	Likely Benign	Likely Benign										0.017	Likely Benign	-0.31	Neutral	0.113	Benign	0.011	Benign	4.29	Benign	0.00	Affected			0.3155	0.4740		1	1	2.7	-27.03
c.236A>T	N79I 2D AIThe SynGAP1 missense variant N79I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375											-3.958	Likely Benign	0.337	Likely Benign	Likely Benign										0.030	Likely Benign	-1.42	Neutral	0.939	Possibly Damaging	0.080	Benign	4.14	Benign	0.00	Affected			0.0572	0.4924		-2	-3	8.0	-0.94
c.2371A>C	K791Q 2D AIThe SynGAP1 missense variant K791Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that K791Q is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-3.418	Likely Benign	0.195	Likely Benign	Likely Benign										0.081	Likely Benign	-0.09	Neutral	0.802	Possibly Damaging	0.335	Benign	4.17	Benign	0.46	Tolerated			0.5322	0.1159	Weaken	1	1	0.4	-0.04
c.2371A>G	K791E 2D AIThe SynGAP1 missense variant K791E is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign; Foldetta results are unavailable. Taken together, the preponderance of evidence supports a benign impact for K791E, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-3.823	Likely Benign	0.465	Ambiguous	Likely Benign										0.053	Likely Benign	-0.58	Neutral	0.451	Benign	0.193	Benign	4.22	Benign	0.65	Tolerated			0.4829	0.0876		0	1	0.4	0.94
c.1071C>G	H357Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H357Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. Based on the uniform predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-4.370	Likely Benign	0.163	Likely Benign	Likely Benign	0.06	Likely Benign	0.2	-0.03	Likely Benign	0.02	Likely Benign	-0.35	Likely Benign	0.025	Likely Benign	1.42	Neutral	0.013	Benign	0.007	Benign	4.49	Benign	1.00	Tolerated			0.1716	0.3850		3	0	-0.3	-9.01
c.2372A>G	K791R 2D AIThe SynGAP1 missense variant K791R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence supports a benign classification for K791R, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-2.359	Likely Benign	0.082	Likely Benign	Likely Benign										0.028	Likely Benign	-0.96	Neutral	0.802	Possibly Damaging	0.249	Benign	4.14	Benign	0.50	Tolerated			0.5520	0.1223	Weaken	3	2	-0.6	28.01
c.2372A>T	K791M 2D AIThe SynGAP1 missense variant K791M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus and high‑accuracy predictions, points to a benign impact for K791M. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-3.898	Likely Benign	0.653	Likely Pathogenic	Likely Benign										0.050	Likely Benign	-1.12	Neutral	0.934	Possibly Damaging	0.558	Possibly Damaging	4.10	Benign	0.04	Affected			0.1642	0.4179		0	-1	5.8	3.02
c.2373G>C	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy predictions (SGM‑Consensus, AlphaMissense‑Optimized uncertain, Foldetta unavailable) lean toward a benign interpretation, with only two pathogenic calls. Thus, based on the current computational evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2373G>T	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy predictions (including the SGM‑Consensus) indicate a benign impact, and there is no conflict with ClinVar status. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2374G>A	E792K 2D AIThe SynGAP1 missense variant E792K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates 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 likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-4.942	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.059	Likely Benign	-2.47	Neutral	0.033	Benign	0.017	Benign	3.90	Benign	0.01	Affected			0.2646	0.7584		0	1	-0.4	-0.94
c.106C>G	H36D 2D AIThe SynGAP1 missense variant H36D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta results are not available for this variant. Overall, the majority of computational evidence indicates that H36D is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-2.859	Likely Benign	0.225	Likely Benign	Likely Benign										0.117	Likely Benign	-1.06	Neutral	0.043	Benign	0.033	Benign	4.21	Benign	0.00	Affected			0.2805	0.3496		1	-1	-0.3	-22.05
c.1081C>A	Q361K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361K is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic outcome. High‑accuracy tools that integrate structural and evolutionary information—AlphaMissense‑Optimized, the SGM‑Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all return benign predictions. No prediction or folding‑stability result is missing or inconclusive. Based on the aggregate evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-5.147	Likely Benign	0.286	Likely Benign	Likely Benign	0.17	Likely Benign	0.0	0.36	Likely Benign	0.27	Likely Benign	-0.44	Likely Benign	0.217	Likely Benign	1.29	Neutral	0.969	Probably Damaging	0.930	Probably Damaging	1.73	Pathogenic	1.00	Tolerated			0.1739	0.4701		1	1	-0.4	0.04
c.2341A>T	M781L 2D AIThe SynGAP1 missense variant M781L is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this benign classification: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this prediction is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625											-2.334	Likely Benign	0.140	Likely Benign	Likely Benign										0.143	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	2.83	Benign	0.88	Tolerated			0.1530	0.3669		4	2	1.9	-18.03
c.2342T>A	M781K 2D AIThe SynGAP1 missense variant M781K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625											-6.321	Likely Benign	0.734	Likely Pathogenic	Likely Benign										0.258	Likely Benign	-1.47	Neutral	0.138	Benign	0.150	Benign	2.72	Benign	0.20	Tolerated			0.1550	0.0688		0	-1	-5.8	-3.02
c.107A>T	H36L 2D AIThe SynGAP1 missense variant H36L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign classification. AlphaMissense‑Optimized also reports benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-2.403	Likely Benign	0.129	Likely Benign	Likely Benign										0.095	Likely Benign	-1.73	Neutral	0.010	Benign	0.011	Benign	4.19	Benign	0.00	Affected			0.1310	0.6111		-2	-3	7.0	-23.98
c.2342T>G	M781R 2D AIThe SynGAP1 missense variant M781R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625											-4.990	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.265	Likely Benign	-1.72	Neutral	0.327	Benign	0.206	Benign	2.71	Benign	0.14	Tolerated			0.1685	0.0837		0	-1	-6.4	24.99
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		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625					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	0.1405	0.2793		1	2	2.6	-18.03
c.107A>G	H36R 2D AIThe SynGAP1 missense variant H36R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-2.513	Likely Benign	0.162	Likely Benign	Likely Benign										0.034	Likely Benign	-0.70	Neutral	0.084	Benign	0.033	Benign	4.25	Benign	0.00	Affected			0.2417	0.3590		2	0	-1.3	19.05
c.2343G>T	M781I 2D AIThe SynGAP1 missense variant M781I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: 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, did not provide a result for this variant. Overall, the evidence strongly suggests that M781I is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625											-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	0.1405	0.2793		1	2	2.6	-18.03
c.2344G>A	D782N 2D AIThe SynGAP1 missense variant D782N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-6.857	Likely Benign	0.766	Likely Pathogenic	Likely Benign										0.131	Likely Benign	-2.26	Neutral	0.995	Probably Damaging	0.950	Probably Damaging	1.98	Pathogenic	0.02	Affected			0.1167	0.6884		2	1	0.0	-0.98
c.2344G>C	D782H 2D AIThe SynGAP1 missense variant D782H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only REVEL predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta data are unavailable. Taken together, the majority of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.528	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.311	Likely Benign	-2.63	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1333	0.7286		1	-1	0.3	22.05
c.2344G>T	D782Y 2D AIThe SynGAP1 missense variant D782Y is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.785	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.382	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0559	0.6202		-4	-3	2.2	48.09
c.2345A>C	D782A 2D AIThe SynGAP1 missense variant D782A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, reports the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Taken together, the preponderance of evidence from multiple in silico predictors and the SGM‑Consensus suggests that D782A is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-7.054	In-Between	0.892	Likely Pathogenic	Ambiguous										0.345	Likely Benign	-3.33	Deleterious	0.990	Probably Damaging	0.932	Probably Damaging	1.95	Pathogenic	0.01	Affected			0.3819	0.6121		0	-2	5.3	-44.01
c.2345A>G	D782G 2D AIThe SynGAP1 missense variant D782G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-6.811	Likely Benign	0.858	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.27	Deleterious	0.995	Probably Damaging	0.950	Probably Damaging	1.95	Pathogenic	0.02	Affected			0.3816	0.6318		1	-1	3.1	-58.04
c.2341A>C	M781L 2D AIThe SynGAP1 missense variant M781L is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625											-2.334	Likely Benign	0.140	Likely Benign	Likely Benign										0.143	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	2.83	Benign	0.88	Tolerated			0.1530	0.3669		4	2	1.9	-18.03
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		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500					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			0.1445	0.4276		-3	-2	8.3	-43.03
c.2336G>C	S779T 2D AIThe SynGAP1 missense variant S779T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. Only two tools—polyPhen‑2 HumDiv and FATHMM—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are not available for this variant. Overall, the consensus of available predictions points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.458	Likely Benign	0.144	Likely Benign	Likely Benign										0.132	Likely Benign	-0.71	Neutral	0.611	Possibly Damaging	0.396	Benign	2.34	Pathogenic	0.79	Tolerated			0.1491	0.6392		1	1	0.1	14.03
c.2336G>T	S779I 2D AIThe SynGAP1 missense variant S779I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy methods give a benign call from AlphaMissense‑Optimized; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-6.261	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.198	Likely Benign	-2.10	Neutral	0.918	Possibly Damaging	0.827	Possibly Damaging	2.28	Pathogenic	0.05	Affected			0.1046	0.6248		-1	-2	5.3	26.08
c.2337C>A	S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.119	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2337C>G	S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2338T>A	S780T 2D AIThe SynGAP1 missense variant S780T is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500											-4.911	Likely Benign	0.157	Likely Benign	Likely Benign										0.048	Likely Benign	-0.63	Neutral	0.951	Possibly Damaging	0.614	Possibly Damaging	2.66	Benign	0.84	Tolerated			0.1445	0.6631		1	1	0.1	14.03
c.1080G>T	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.2338T>G	S780A 2D AIThe SynGAP1 missense variant S780A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S780A is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500											-5.627	Likely Benign	0.164	Likely Benign	Likely Benign										0.072	Likely Benign	-0.40	Neutral	0.798	Possibly Damaging	0.340	Benign	2.69	Benign	0.74	Tolerated			0.4936	0.5522		1	1	2.6	-16.00
c.2339C>A	S780Y 2D AIThe SynGAP1 missense variant S780Y is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500											-7.682	In-Between	0.656	Likely Pathogenic	Likely Benign										0.091	Likely Benign	-1.71	Neutral	0.995	Probably Damaging	0.925	Probably Damaging	2.61	Benign	0.11	Tolerated			0.0810	0.6428		-3	-2	-0.5	76.10
c.1080G>C	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and SIFT. In contrast, a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus remains Likely Pathogenic, while Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360D. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.2339C>T	S780F 2D AIThe SynGAP1 missense variant S780F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is also unavailable for this variant. Overall, the majority of available predictions (five benign vs. four pathogenic) lean toward a benign impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500											-8.055	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign										0.104	Likely Benign	-1.42	Neutral	0.995	Probably Damaging	0.925	Probably Damaging	2.61	Benign	0.10	Tolerated			0.0768	0.6706		-3	-2	3.6	60.10
c.233G>A	R78H 2D AIThe SynGAP1 R78H missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-4.851	Likely Benign	0.250	Likely Benign	Likely Benign										0.070	Likely Benign	-1.38	Neutral	0.908	Possibly Damaging	0.108	Benign	3.83	Benign	0.00	Affected			0.2453	0.1601		2	0	1.3	-19.05
c.233G>C	R78P 2D AIThe SynGAP1 missense variant R78P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R78P, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-4.049	Likely Benign	0.611	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-1.72	Neutral	0.817	Possibly Damaging	0.123	Benign	3.82	Benign	0.00	Affected			0.2083	0.3750		0	-2	2.9	-59.07
c.2345A>T	D782V 2D AIThe SynGAP1 missense variant D782V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which reports “Likely Pathogenic”). The high‑accuracy AlphaMissense‑Optimized tool yields an uncertain result, and the Foldetta stability assessment is unavailable. Overall, the consensus of the available predictions strongly favors a pathogenic effect for D782V. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.250	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.979	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0803	0.6477		-2	-3	7.7	-15.96
c.2346C>A	D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-4.447	Likely Benign	0.486	Ambiguous	Likely Benign										0.127	Likely Benign	-1.75	Neutral	0.561	Possibly Damaging	0.207	Benign	2.14	Pathogenic	0.01	Affected			0.1351	0.7036		3	2	0.0	14.03
c.2346C>G	D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a majority benign vote (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-4.447	Likely Benign	0.486	Ambiguous	Likely Benign										0.127	Likely Benign	-1.75	Neutral	0.561	Possibly Damaging	0.207	Benign	2.14	Pathogenic	0.01	Affected			0.1351	0.7036		3	2	0.0	14.03
c.2353C>A	R785S 2D AIThe SynGAP1 missense variant R785S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-2.926	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-2.93	Deleterious	0.980	Probably Damaging	0.765	Possibly Damaging	2.34	Pathogenic	0.01	Affected			0.3523	0.3800		0	-1	3.7	-69.11
c.2353C>G	R785G 2D AIThe SynGAP1 missense variant R785G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further reveal that AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus again suggests pathogenicity; Foldetta stability analysis is not available for this variant. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the SGM‑Consensus result. Because the variant is not present in ClinVar, there is no existing clinical classification to contradict; thus, based on the available computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-3.684	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.44	Deleterious	0.980	Probably Damaging	0.818	Possibly Damaging	2.25	Pathogenic	0.00	Affected			0.3695	0.3686		-3	-2	4.1	-99.14
c.1079A>C	E360A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS. All other evaluated tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Because the majority of consensus tools predict pathogenicity and no ClinVar entry contradicts this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-13.229	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.1	1.72	Ambiguous	1.55	Ambiguous	0.39	Likely Benign	0.545	Likely Pathogenic	-5.52	Deleterious	0.997	Probably Damaging	0.980	Probably Damaging	1.63	Pathogenic	0.01	Affected			0.4295	0.8243		0	-1	5.3	-58.04
c.1078G>C	E360Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and premPS, while a majority of tools predict a pathogenic outcome: SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360Q, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-11.012	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.1	1.38	Ambiguous	0.97	Ambiguous	-0.02	Likely Benign	0.343	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.61	Pathogenic	0.03	Affected			0.1824	0.8282		2	2	0.0	-0.98
c.2354G>T	R785L 2D AIThe SynGAP1 missense variant R785L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-4.457	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.158	Likely Benign	-4.43	Deleterious	0.960	Probably Damaging	0.627	Possibly Damaging	2.26	Pathogenic	0.01	Affected			0.1993	0.4539		-3	-2	8.3	-43.03
c.2356C>A	L786I 2D AIThe SynGAP1 missense variant L786I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence, especially from the high‑accuracy methods, points to a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-5.464	Likely Benign	0.215	Likely Benign	Likely Benign										0.087	Likely Benign	-1.12	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1056	0.4199		2	2	0.7	0.00
c.2356C>G	L786V 2D AIThe SynGAP1 missense variant L786V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently has no classification for L786V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.607	Likely Benign	0.310	Likely Benign	Likely Benign										0.099	Likely Benign	-1.66	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1683	0.4049		2	1	0.4	-14.03
c.1076C>G	T359R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T359R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign effects include REVEL, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Uncertain results come from FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, more tools favor a benign outcome, but a significant minority predict pathogenicity, leaving the variant’s clinical significance unresolved. The variant is most likely benign based on the prevailing predictions, and this does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-8.675	Likely Pathogenic	0.402	Ambiguous	Likely Benign	-0.74	Ambiguous	0.1	-0.20	Likely Benign	-0.47	Likely Benign	0.54	Ambiguous	0.157	Likely Benign	-2.86	Deleterious	0.627	Possibly Damaging	0.091	Benign	1.75	Pathogenic	0.23	Tolerated			0.1323	0.3748		-1	-1	-3.8	55.08
c.2356C>T	L786F 2D AIThe SynGAP1 missense variant L786F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.949	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.112	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.00	Affected			0.0765	0.3847		2	0	-1.0	34.02
c.2357T>A	L786H 2D AIThe SynGAP1 missense variant L786H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Grouping by agreement, two tools predict benign, seven predict pathogenic, and AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, but 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 majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-5.892	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.168	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1309	0.1214		-2	-3	-7.0	23.98
c.1076C>A	T359K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T359K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. The remaining tools—FoldX, Rosetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign classification, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-10.822	Likely Pathogenic	0.517	Ambiguous	Likely Benign	-0.65	Ambiguous	0.1	0.66	Ambiguous	0.01	Likely Benign	0.75	Ambiguous	0.163	Likely Benign	-2.23	Neutral	0.255	Benign	0.045	Benign	1.79	Pathogenic	0.24	Tolerated			0.1618	0.3483		0	-1	-3.2	27.07
c.2357T>G	L786R 2D AIThe SynGAP1 missense variant L786R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, and the lack of a Foldetta result does not alter this conclusion. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.989	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.169	Likely Benign	-3.07	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1403	0.1288		-3	-2	-8.3	43.03
c.2351C>T	A784V 2D AIThe SynGAP1 missense variant A784V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the collective evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625											-3.901	Likely Benign	0.205	Likely Benign	Likely Benign										0.056	Likely Benign	-0.97	Neutral	0.126	Benign	0.138	Benign	2.72	Benign	0.26	Tolerated			0.1150	0.5803		0	0	2.4	28.05
c.1079A>G	E360G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: premPS is the only tool that predicts a benign outcome, whereas all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the substitution as pathogenic. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized returns a pathogenic prediction; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic impact for E360G, and this conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-13.972	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	2.55	Destabilizing	0.1	2.99	Destabilizing	2.77	Destabilizing	0.31	Likely Benign	0.569	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	1.68	Pathogenic	0.04	Affected			0.2993	0.6935		0	-2	3.1	-72.06
c.2347A>C	M783L 2D AIThe SynGAP1 missense variant M783L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the collective evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-1.915	Likely Benign	0.138	Likely Benign	Likely Benign										0.108	Likely Benign	-0.48	Neutral	0.004	Benign	0.006	Benign	2.99	Benign	1.00	Tolerated			0.1727	0.4461		4	2	1.9	-18.03
c.107A>C	H36P 2D AIThe SynGAP1 missense variant H36P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-2.285	Likely Benign	0.066	Likely Benign	Likely Benign										0.171	Likely Benign	-1.23	Neutral	0.182	Benign	0.046	Benign	4.16	Benign	0.00	Affected			0.2097	0.4723		0	-2	1.6	-40.02
c.2347A>T	M783L 2D AIThe SynGAP1 missense variant M783L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the change as benign. No tool in the dataset predicts pathogenicity. High‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability approach, has no available result for this variant. Overall, the collective evidence strongly supports a benign interpretation, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-1.915	Likely Benign	0.138	Likely Benign	Likely Benign										0.110	Likely Benign	-0.48	Neutral	0.004	Benign	0.006	Benign	2.99	Benign	1.00	Tolerated			0.1727	0.4461		4	2	1.9	-18.03
c.2348T>A	M783K 2D AIThe SynGAP1 missense variant M783K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-4.923	Likely Benign	0.693	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.70	Deleterious	0.925	Possibly Damaging	0.424	Benign	2.66	Benign	0.01	Affected			0.1730	0.0912		0	-1	-5.8	-3.02
c.2348T>C	M783T 2D AIThe SynGAP1 missense variant M783T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the high‑accuracy consensus points to a benign effect, with no conflict with ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-4.064	Likely Benign	0.299	Likely Benign	Likely Benign										0.111	Likely Benign	-2.08	Neutral	0.625	Possibly Damaging	0.265	Benign	2.69	Benign	0.03	Affected			0.2217	0.2308		-1	-1	-2.6	-30.09
c.2348T>G	M783R 2D AIThe SynGAP1 missense variant M783R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-3.849	Likely Benign	0.655	Likely Pathogenic	Likely Benign										0.208	Likely Benign	-2.69	Deleterious	0.925	Possibly Damaging	0.529	Possibly Damaging	2.66	Benign	0.01	Affected			0.1815	0.0893		0	-1	-6.4	24.99
c.2349G>C	M783I 2D AIThe SynGAP1 missense variant M783I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Consensus from multiple in‑silico predictors classifies the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all return benign scores, and AlphaMissense‑Optimized also predicts a benign effect. No tool in the set indicates pathogenicity. The high‑accuracy assessments corroborate this view: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and Foldetta data are unavailable. Consequently, the aggregate evidence strongly supports a benign interpretation for M783I, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-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	0.1540	0.3710		1	2	2.6	-18.03
c.2349G>T	M783I 2D AIThe SynGAP1 missense variant M783I is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect. Benign calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the computational evidence strongly supports a benign classification for M783I, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-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	0.1540	0.3710		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		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625					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	0.1493	0.6659		1	0	-2.5	30.03
c.1079A>T	E360V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the overwhelming majority of reliable predictors classify E360V as pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-14.388	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.11	Ambiguous	1.06	Ambiguous	0.03	Likely Benign	0.627	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.57	Pathogenic	0.00	Affected			0.1143	0.8670		-2	-2	7.7	-29.98
c.2350G>T	A784S 2D AIThe SynGAP1 missense variant A784S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625											-2.233	Likely Benign	0.094	Likely Benign	Likely Benign										0.027	Likely Benign	0.41	Neutral	0.004	Benign	0.010	Benign	2.72	Benign	0.67	Tolerated			0.2624	0.5171		1	1	-2.6	16.00
c.2351C>A	A784D 2D AIThe SynGAP1 missense variant A784D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625											-3.784	Likely Benign	0.766	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-1.21	Neutral	0.411	Benign	0.237	Benign	2.68	Benign	0.16	Tolerated			0.1824	0.2193		0	-2	-5.3	44.01
c.1075A>T	T359S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T359S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only FATHMM predicts a pathogenic outcome, while FoldX, Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is uncertain. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-4.624	Likely Benign	0.091	Likely Benign	Likely Benign	0.50	Ambiguous	0.0	0.73	Ambiguous	0.62	Ambiguous	0.66	Ambiguous	0.100	Likely Benign	-1.87	Neutral	0.146	Benign	0.024	Benign	1.76	Pathogenic	0.27	Tolerated			0.3637	0.4996		1	1	-0.1	-14.03
c.2575A>T	S859C 2D AIThe SynGAP1 missense variant S859C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN reports the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.268	Likely Pathogenic	0.136	Likely Benign	Likely Benign										0.195	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.94	Benign	0.03	Affected			0.1046	0.6153		0	-1	3.3	16.06
c.2581T>A	S861T 2D AIThe SynGAP1 missense variant S861T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. AlphaMissense‑Optimized likewise predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-4.462	Likely Benign	0.096	Likely Benign	Likely Benign										0.022	Likely Benign	-0.83	Neutral	0.043	Benign	0.026	Benign	3.99	Benign	0.14	Tolerated			0.1262	0.6245		1	1	0.1	14.03
c.1017G>T	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact for K339N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.2581T>C	S861P 2D AIThe SynGAP1 missense variant S861P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for S861P, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-4.256	Likely Benign	0.107	Likely Benign	Likely Benign										0.116	Likely Benign	-1.65	Neutral	0.960	Probably Damaging	0.761	Possibly Damaging	3.93	Benign	0.13	Tolerated			0.1830	0.6011		1	-1	-0.8	10.04
c.2581T>G	S861A 2D AIThe SynGAP1 missense variant S861A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-5.059	Likely Benign	0.092	Likely Benign	Likely Benign										0.043	Likely Benign	-1.02	Neutral	0.409	Benign	0.172	Benign	4.08	Benign	0.48	Tolerated			0.4541	0.5401		1	1	2.6	-16.00
c.2582C>G	S861W 2D AIThe SynGAP1 missense variant S861W has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority of the four high‑accuracy tools) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-8.538	Likely Pathogenic	0.585	Likely Pathogenic	Likely Benign										0.267	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	3.89	Benign	0.01	Affected			0.0874	0.6247		-2	-3	-0.1	99.14
c.1017G>C	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for K339N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.2584A>C	N862H 2D AIThe SynGAP1 missense variant at residue 862 (N862H) is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for this variant, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-4.633	Likely Benign	0.174	Likely Benign	Likely Benign										0.178	Likely Benign	-1.46	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.02	Benign	0.11	Tolerated			0.1578	0.7435		2	1	0.3	23.04
c.2584A>G	N862D 2D AIThe SynGAP1 missense variant N862D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-5.255	Likely Benign	0.323	Likely Benign	Likely Benign										0.144	Likely Benign	-1.22	Neutral	0.995	Probably Damaging	0.926	Probably Damaging	4.06	Benign	0.51	Tolerated			0.1786	0.4764		2	1	0.0	0.98
c.2584A>T	N862Y 2D AIThe SynGAP1 missense variant N862Y is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence—especially the high‑accuracy consensus—suggests the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-8.200	Likely Pathogenic	0.485	Ambiguous	Likely Benign										0.216	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	4.01	Benign	0.06	Tolerated			0.0871	0.6246		-2	-2	2.2	49.07
c.1016A>T	K339M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339M missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX and premPS, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K339M. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-13.387	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.0	0.88	Ambiguous	0.56	Ambiguous	-0.37	Likely Benign	0.575	Likely Pathogenic	-4.95	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	1.92	Pathogenic	0.01	Affected			0.0967	0.3541		0	-1	5.8	3.02
c.2585A>C	N862T 2D AIThe SynGAP1 missense variant at residue 862 (Asn→Thr) is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates “Likely Benign.” In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-5.623	Likely Benign	0.170	Likely Benign	Likely Benign										0.122	Likely Benign	-1.60	Neutral	0.995	Probably Damaging	0.946	Probably Damaging	4.09	Benign	0.19	Tolerated			0.1542	0.7704		0	0	2.8	-13.00
c.2585A>G	N862S 2D AIThe SynGAP1 missense variant at residue 862 (N862S) is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-3.650	Likely Benign	0.070	Likely Benign	Likely Benign										0.106	Likely Benign	-1.40	Neutral	0.966	Probably Damaging	0.848	Possibly Damaging	4.13	Benign	0.36	Tolerated			0.3809	0.7198		1	1	2.7	-27.03
c.1018G>C	A340P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A340P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The high‑accuracy predictors—AlphaMissense‑Optimized, the SGM‑Consensus, and Foldetta—each report a benign outcome. No prediction or folding‑stability result is missing or inconclusive; all available evidence points to a benign impact. Consequently, the variant is most likely benign based on the aggregate predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.390993	Structured	0.410781	Uncertain	0.558	0.485	0.250											-4.983	Likely Benign	0.264	Likely Benign	Likely Benign	0.32	Likely Benign	0.5	-0.58	Ambiguous	-0.13	Likely Benign	0.46	Likely Benign	0.279	Likely Benign	-1.48	Neutral	0.891	Possibly Damaging	0.575	Possibly Damaging	1.91	Pathogenic	0.25	Tolerated			0.2178	0.5468		1	-1	-3.4	26.04
c.257T>G	V86G 2D AIThe SynGAP1 missense variant V86G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which evaluates protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence (five pathogenic versus four benign predictions) indicates that V86G is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-4.212	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.130	Likely Benign	-2.50	Deleterious	0.307	Benign	0.824	Possibly Damaging	3.74	Benign	0.00	Affected			0.2321	0.2547		-1	-3	-4.6	-42.08
c.2576G>A	S859N 2D AIThe SynGAP1 missense variant S859N is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.184	Likely Pathogenic	0.225	Likely Benign	Likely Benign										0.142	Likely Benign	-0.62	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	3.99	Benign	0.29	Tolerated			0.1221	0.5226		1	1	-2.7	27.03
c.2576G>C	S859T 2D AIThe SynGAP1 missense variant S859T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. ESM1b is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.155	In-Between	0.089	Likely Benign	Likely Benign										0.154	Likely Benign	-0.97	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.02	Benign	0.24	Tolerated			0.1345	0.6434		1	1	0.1	14.03
c.2576G>T	S859I 2D AIThe SynGAP1 missense variant S859I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar record exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.342	Likely Pathogenic	0.351	Ambiguous	Likely Benign										0.256	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	3.99	Benign	0.02	Affected			0.1094	0.5867		-1	-2	5.3	26.08
c.2577T>A	S859R 2D AIThe SynGAP1 missense variant S859R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.810	In-Between	0.844	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.42	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.00	Benign	0.06	Tolerated			0.0945	0.4061		0	-1	-3.7	69.11
c.2577T>G	S859R 2D AIThe SynGAP1 missense variant S859R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized remains uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign (two benign versus one pathogenic vote). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.810	In-Between	0.844	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.42	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.00	Benign	0.06	Tolerated			0.0945	0.4061		0	-1	-3.7	69.11
c.2578G>C	V860L 2D AIThe SynGAP1 missense variant V860L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.053	Likely Benign	0.123	Likely Benign	Likely Benign										0.028	Likely Benign	-0.89	Neutral	0.124	Benign	0.037	Benign	4.17	Benign	0.00	Affected			0.1052	0.5446		2	1	-0.4	14.03
c.2578G>T	V860F 2D AIThe SynGAP1 missense variant V860F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-4.576	Likely Benign	0.143	Likely Benign	Likely Benign										0.101	Likely Benign	-2.25	Neutral	0.846	Possibly Damaging	0.522	Possibly Damaging	4.09	Benign	0.00	Affected			0.0717	0.4138		-1	-1	-1.4	48.04
c.2579T>A	V860D 2D AIThe SynGAP1 missense variant V860D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-4.310	Likely Benign	0.590	Likely Pathogenic	Likely Benign										0.164	Likely Benign	-1.98	Neutral	0.971	Probably Damaging	0.690	Possibly Damaging	4.08	Benign	0.00	Affected			0.1382	0.1047		-2	-3	-7.7	15.96
c.2579T>C	V860A 2D AIThe SynGAP1 missense variant V860A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT predicts pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for V860A, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.379	Likely Benign	0.161	Likely Benign	Likely Benign										0.223	Likely Benign	-0.91	Neutral	0.393	Benign	0.185	Benign	4.20	Benign	0.00	Affected			0.3215	0.2723		0	0	-2.4	-28.05
c.2579T>G	V860G 2D AIThe SynGAP1 missense variant V860G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: the benign group includes REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic group contains only SIFT. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, while Foldetta results are unavailable. Overall, the collective evidence indicates that V860G is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.471	Likely Benign	0.173	Likely Benign	Likely Benign										0.198	Likely Benign	-1.54	Neutral	0.012	Benign	0.009	Benign	4.11	Benign	0.00	Affected			0.2312	0.2547		-1	-3	-4.6	-42.08
c.257T>A	V86D 2D AIThe SynGAP1 missense variant V86D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on benign impact include REVEL, PROVEAN, and FATHMM, whereas those that agree on pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans benign (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, whereas the high‑accuracy consensus suggests benign. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for V86D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-7.141	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.147	Likely Benign	-2.38	Neutral	0.824	Possibly Damaging	0.485	Possibly Damaging	3.73	Benign	0.00	Affected			0.1590	0.1047		-2	-3	-7.7	15.96
c.257T>C	V86A 2D AIThe SynGAP1 missense variant V86A has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Pathogenic predictions arise from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight a split: AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it 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 tools (six benign vs. three pathogenic) suggest the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-3.022	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.059	Likely Benign	-1.35	Neutral	0.267	Benign	0.153	Benign	3.80	Benign	0.00	Affected			0.3205	0.2723		0	0	-2.4	-28.05
c.2585A>T	N862I 2D AIThe SynGAP1 missense variant N862I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; AlphaMissense‑Default is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority (2 pathogenic vs. 1 benign, 1 uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions support a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-8.702	Likely Pathogenic	0.561	Ambiguous	Likely Benign										0.195	Likely Benign	-3.19	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	4.03	Benign	0.03	Affected			0.0844	0.6443		-2	-3	8.0	-0.94
c.2586C>A	N862K 2D AIThe SynGAP1 missense variant N862K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-7.000	In-Between	0.766	Likely Pathogenic	Likely Benign										0.084	Likely Benign	-1.87	Neutral	0.995	Probably Damaging	0.946	Probably Damaging	4.10	Benign	0.20	Tolerated			0.2313	0.5469		1	0	-0.4	14.07
c.2586C>G	N862K 2D AIThe SynGAP1 missense variant N862K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-7.000	In-Between	0.766	Likely Pathogenic	Likely Benign										0.084	Likely Benign	-1.87	Neutral	0.995	Probably Damaging	0.946	Probably Damaging	4.10	Benign	0.20	Tolerated			0.2313	0.5469		1	0	-0.4	14.07
c.2593G>A	A865T 2D AIThe SynGAP1 missense variant A865T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-4.435	Likely Benign	0.078	Likely Benign	Likely Benign										0.026	Likely Benign	-0.84	Neutral	0.440	Benign	0.197	Benign	2.72	Benign	0.29	Tolerated			0.1263	0.6083		1	0	-2.5	30.03
c.2593G>C	A865P 2D AIThe SynGAP1 missense variant A865P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-4.178	Likely Benign	0.139	Likely Benign	Likely Benign										0.077	Likely Benign	-0.66	Neutral	0.918	Possibly Damaging	0.697	Possibly Damaging	2.67	Benign	0.27	Tolerated			0.1707	0.4690		1	-1	-3.4	26.04
c.2593G>T	A865S 2D AIThe SynGAP1 missense variant A865S is reported as “Likely Benign” in SGM‑Consensus and has no ClinVar entry or gnomAD allele. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-3.102	Likely Benign	0.073	Likely Benign	Likely Benign										0.050	Likely Benign	0.20	Neutral	0.009	Benign	0.019	Benign	2.78	Benign	0.52	Tolerated			0.2314	0.4876		1	1	-2.6	16.00
c.2594C>A	A865D 2D AIThe SynGAP1 missense variant A865D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-4.635	Likely Benign	0.515	Ambiguous	Likely Benign										0.123	Likely Benign	-0.57	Neutral	0.611	Possibly Damaging	0.346	Benign	2.71	Benign	0.36	Tolerated			0.1563	0.1560		0	-2	-5.3	44.01
c.2594C>G	A865G 2D AIThe SynGAP1 missense variant A865G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-3.412	Likely Benign	0.107	Likely Benign	Likely Benign										0.027	Likely Benign	-0.74	Neutral	0.009	Benign	0.019	Benign	2.69	Benign	0.51	Tolerated			0.2344	0.4683		1	0	-2.2	-14.03
c.1014C>G	D338E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D338E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign classification, while Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No other tools provide conflicting evidence. Based on the preponderance of benign predictions and the lack of pathogenic support from high‑accuracy methods, the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-5.264	Likely Benign	0.254	Likely Benign	Likely Benign	0.85	Ambiguous	0.3	0.31	Likely Benign	0.58	Ambiguous	-0.01	Likely Benign	0.080	Likely Benign	-1.95	Neutral	0.002	Benign	0.005	Benign	1.85	Pathogenic	0.55	Tolerated			0.1584	0.5397		3	2	0.0	14.03
c.2594C>T	A865V 2D AIThe SynGAP1 missense variant A865V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the computational evidence overwhelmingly suggests that A865V is most likely benign, and this assessment is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250											-4.639	Likely Benign	0.134	Likely Benign	Likely Benign										0.049	Likely Benign	-1.42	Neutral	0.611	Possibly Damaging	0.419	Benign	2.70	Benign	0.37	Tolerated			0.1145	0.6031		0	0	2.4	28.05
c.1014C>A	D338E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D338E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign classification, while Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No other tools provide conflicting evidence. Based on the preponderance of benign predictions and the lack of pathogenic support from high‑accuracy methods, the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-5.264	Likely Benign	0.254	Likely Benign	Likely Benign	0.85	Ambiguous	0.3	0.31	Likely Benign	0.58	Ambiguous	-0.01	Likely Benign	0.080	Likely Benign	-1.95	Neutral	0.002	Benign	0.005	Benign	1.85	Pathogenic	0.55	Tolerated			0.1584	0.5397		3	2	0.0	14.03
c.2596G>C	V866L 2D AIThe SynGAP1 missense variant V866L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.638070	Binding	0.266	0.788	0.250											-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	0.0836	0.4660		2	1	-0.4	14.03
c.1013A>T	D338V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D338V missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No prediction or folding‑stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-11.494	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	1.64	Ambiguous	0.2	1.08	Ambiguous	1.36	Ambiguous	0.23	Likely Benign	0.553	Likely Pathogenic	-6.79	Deleterious	0.891	Possibly Damaging	0.492	Possibly Damaging	1.73	Pathogenic	0.01	Affected			0.0879	0.5745		-2	-3	7.7	-15.96
c.2597T>A	V866E 2D AIThe SynGAP1 missense variant V866E is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the SGM consensus and AlphaMissense‑Optimized—points to a benign effect, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.638070	Binding	0.266	0.788	0.250											-3.917	Likely Benign	0.422	Ambiguous	Likely Benign										0.157	Likely Benign	-2.09	Neutral	0.998	Probably Damaging	0.939	Probably Damaging	2.72	Benign	0.05	Affected			0.0996	0.1629		-2	-2	-7.7	29.98
c.2597T>G	V866G 2D AIThe SynGAP1 missense variant V866G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for V866G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.638070	Binding	0.266	0.788	0.250											-1.519	Likely Benign	0.136	Likely Benign	Likely Benign										0.124	Likely Benign	-2.30	Neutral	0.912	Possibly Damaging	0.993	Probably Damaging	2.69	Benign	0.07	Tolerated			0.2548	0.2157		-1	-3	-4.6	-42.08
c.1015A>C	K339Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evaluated tools (8 pathogenic vs. 4 benign) indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.952	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	0.06	Likely Benign	0.0	-0.50	Ambiguous	-0.22	Likely Benign	-0.02	Likely Benign	0.458	Likely Benign	-3.06	Deleterious	0.982	Probably Damaging	0.824	Possibly Damaging	1.90	Pathogenic	0.04	Affected			0.4041	0.1012		1	1	0.4	-0.04
c.2591C>G	A864G 2D AIThe SynGAP1 missense variant A864G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the change as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign effect, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250											-3.662	Likely Benign	0.080	Likely Benign	Likely Benign										0.024	Likely Benign	-0.55	Neutral	0.003	Benign	0.004	Benign	2.55	Benign	0.16	Tolerated			0.2383	0.5388		1	0	-2.2	-14.03
c.2587C>A	L863M 2D AIThe SynGAP1 missense variant L863M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available, so they do not influence the overall assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-5.137	Likely Benign	0.135	Likely Benign	Likely Benign										0.111	Likely Benign	-0.21	Neutral	0.999	Probably Damaging	0.990	Probably Damaging	4.04	Benign	0.28	Tolerated			0.0811	0.3922		4	2	-1.9	18.03
c.1016A>G	K339R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. No predictions or stability results are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-5.773	Likely Benign	0.120	Likely Benign	Likely Benign	-0.15	Likely Benign	0.1	0.46	Likely Benign	0.16	Likely Benign	0.08	Likely Benign	0.134	Likely Benign	-2.05	Neutral	0.046	Benign	0.040	Benign	1.94	Pathogenic	0.48	Tolerated			0.4197	0.0976		3	2	-0.6	28.01
c.2587C>G	L863V 2D AIThe SynGAP1 missense variant L863V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for the L863V variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-3.651	Likely Benign	0.107	Likely Benign	Likely Benign										0.103	Likely Benign	-0.72	Neutral	0.995	Probably Damaging	0.926	Probably Damaging	4.09	Benign	0.21	Tolerated			0.1655	0.3544		2	1	0.4	-14.03
c.2588T>A	L863Q 2D AIThe SynGAP1 missense variant L863Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple independent predictors points to a benign classification for L863Q, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-6.334	Likely Benign	0.279	Likely Benign	Likely Benign										0.135	Likely Benign	-0.68	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.02	Benign	0.23	Tolerated			0.1100	0.1305		-2	-2	-7.3	14.97
c.2588T>C	L863P 2D AIThe SynGAP1 missense variant L863P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-4.760	Likely Benign	0.234	Likely Benign	Likely Benign										0.202	Likely Benign	-0.78	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.01	Benign	0.12	Tolerated			0.3520	0.1458		-3	-3	-5.4	-16.04
c.2588T>G	L863R 2D AIThe SynGAP1 missense variant L863R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-6.402	Likely Benign	0.488	Ambiguous	Likely Benign										0.129	Likely Benign	-1.36	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.02	Benign	0.09	Tolerated			0.1234	0.0947		-3	-2	-8.3	43.03
c.2590G>A	A864T 2D AIThe SynGAP1 missense variant A864T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250											-4.314	Likely Benign	0.077	Likely Benign	Likely Benign										0.016	Likely Benign	-1.00	Neutral	0.224	Benign	0.113	Benign	2.55	Benign	0.10	Tolerated			0.1504	0.7485		1	0	-2.5	30.03
c.1016A>C	K339T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools are split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further highlight this discordance: the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect, whereas Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign impact. AlphaMissense‑Optimized returned an uncertain result and is treated as unavailable. Overall, the majority of robust predictors lean toward pathogenicity, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.061	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.10	Likely Benign	0.21	Likely Benign	-0.04	Likely Benign	0.512	Likely Pathogenic	-4.73	Deleterious	0.991	Probably Damaging	0.795	Possibly Damaging	1.94	Pathogenic	0.10	Tolerated			0.1900	0.3020		0	-1	3.2	-27.07
c.1015A>G	K339E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-14.284	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.13	Likely Benign	0.1	-0.03	Likely Benign	0.05	Likely Benign	0.40	Likely Benign	0.482	Likely Benign	-3.00	Deleterious	0.939	Possibly Damaging	0.670	Possibly Damaging	1.92	Pathogenic	0.03	Affected			0.3421	0.0882		0	1	0.4	0.94
c.2590G>C	A864P 2D AIThe SynGAP1 missense variant A864P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250											-3.665	Likely Benign	0.093	Likely Benign	Likely Benign										0.067	Likely Benign	-0.12	Neutral	0.586	Possibly Damaging	0.211	Benign	2.60	Benign	0.09	Tolerated			0.1941	0.5746		1	-1	-3.4	26.04
c.2590G>T	A864S 2D AIThe SynGAP1 missense variant A864S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250											-3.169	Likely Benign	0.068	Likely Benign	Likely Benign										0.035	Likely Benign	0.08	Neutral	0.112	Benign	0.039	Benign	2.50	Benign	0.16	Tolerated			0.2792	0.6196		1	1	-2.6	16.00
c.2591C>A	A864E 2D AIThe SynGAP1 missense variant A864E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, which evaluates protein‑folding stability, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250											-5.508	Likely Benign	0.350	Ambiguous	Likely Benign										0.153	Likely Benign	0.10	Neutral	0.138	Benign	0.070	Benign	2.45	Pathogenic	0.04	Affected			0.1204	0.2037		0	-1	-5.3	58.04
c.2599G>A	G867R 2D AIThe SynGAP1 missense variant G867R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250											-3.569	Likely Benign	0.755	Likely Pathogenic	Likely Benign										0.131	Likely Benign	-1.76	Neutral	0.997	Probably Damaging	0.943	Probably Damaging	2.70	Benign	0.05	Affected	3.82	4	0.0886	0.4494		-2	-3	-4.1	99.14
c.2554G>T	G852C 2D AIThe SynGAP1 missense variant G852C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and Foldetta results are unavailable. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and AlphaMissense‑Optimized independently predicts a benign outcome. With the majority of evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625											-7.462	In-Between	0.107	Likely Benign	Likely Benign										0.132	Likely Benign	-1.75	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.01	Affected			0.1278	0.4808		-3	-3	2.9	46.09
c.1021G>C	G341R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G341R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, polyPhen‑2 HumVar, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus (Likely Pathogenic), polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts a likely pathogenic outcome, while Foldetta predicts a benign effect; AlphaMissense‑Optimized remains inconclusive. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign, though the evidence is not definitive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-8.263	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.2	-1.25	Ambiguous	-0.49	Likely Benign	0.18	Likely Benign	0.379	Likely Benign	-1.03	Neutral	0.801	Possibly Damaging	0.417	Benign	0.34	Pathogenic	0.17	Tolerated			0.0838	0.3618		-3	-2	-4.1	99.14
c.2561G>C	R854P 2D AIThe SynGAP1 missense variant R854P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R854P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750											-2.627	Likely Benign	0.166	Likely Benign	Likely Benign										0.166	Likely Benign	-1.02	Neutral	0.998	Probably Damaging	0.939	Probably Damaging	4.06	Benign	0.03	Affected			0.2263	0.5163		0	-2	2.9	-59.07
c.2561G>T	R854L 2D AIThe SynGAP1 missense variant R854L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R854L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750											-2.573	Likely Benign	0.167	Likely Benign	Likely Benign										0.131	Likely Benign	-1.78	Neutral	0.960	Probably Damaging	0.765	Possibly Damaging	4.11	Benign	0.03	Affected			0.1875	0.5223		-3	-2	8.3	-43.03
c.2563C>A	L855I 2D AIThe SynGAP1 missense variant L855I is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess functional impact all converge on a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool in the dataset indicates pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-4.721	Likely Benign	0.093	Likely Benign	Likely Benign										0.071	Likely Benign	-0.63	Neutral	0.004	Benign	0.008	Benign	4.08	Benign	0.35	Tolerated			0.0981	0.3893		2	2	0.7	0.00
c.1021G>A	G341S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G341S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Predictions that are inconclusive or uncertain are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence points to a benign impact for G341S, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-3.206	Likely Benign	0.090	Likely Benign	Likely Benign	0.41	Likely Benign	0.3	-1.46	Ambiguous	-0.53	Ambiguous	-0.67	Ambiguous	0.343	Likely Benign	0.73	Neutral	0.454	Possibly Damaging	0.192	Benign	0.37	Pathogenic	0.72	Tolerated			0.2416	0.4215		1	0	-0.4	30.03
c.2563C>G	L855V 2D AIThe SynGAP1 missense variant L855V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-3.866	Likely Benign	0.077	Likely Benign	Likely Benign										0.086	Likely Benign	-0.71	Neutral	0.059	Benign	0.037	Benign	4.10	Benign	0.56	Tolerated			0.1621	0.3731		2	1	0.4	-14.03
c.2563C>T	L855F 2D AIThe SynGAP1 missense variant L855F is predicted to be benign by all evaluated in‑silico tools. Consensus predictions from **SGM‑Consensus** (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classify the variant as *Likely Benign*. High‑accuracy predictors **AlphaMissense‑Optimized** also report a benign effect. Other pathogenicity predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default—uniformly predict benign. No tools predict pathogenicity. **Foldetta**, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its stability impact remains unknown. The variant is not listed in ClinVar and has no entry in gnomAD, so no population frequency or clinical annotation is available. Based on the unanimous benign predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-4.985	Likely Benign	0.106	Likely Benign	Likely Benign										0.091	Likely Benign	-1.86	Neutral	0.411	Benign	0.187	Benign	4.00	Benign	0.12	Tolerated			0.0700	0.3529		2	0	-1.0	34.02
c.2564T>A	L855H 2D AIThe SynGAP1 missense variant L855H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-3.224	Likely Benign	0.148	Likely Benign	Likely Benign										0.114	Likely Benign	-2.07	Neutral	0.938	Possibly Damaging	0.690	Possibly Damaging	3.96	Benign	0.01	Affected			0.1137	0.1313		-2	-3	-7.0	23.98
c.2564T>C	L855P 2D AIThe SynGAP1 missense variant L855P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-2.434	Likely Benign	0.092	Likely Benign	Likely Benign										0.116	Likely Benign	-1.19	Neutral	0.586	Possibly Damaging	0.377	Benign	3.97	Benign	0.14	Tolerated			0.3633	0.1805		-3	-3	-5.4	-16.04
c.2564T>G	L855R 2D AIThe SynGAP1 missense variant L855R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-3.703	Likely Benign	0.229	Likely Benign	Likely Benign										0.086	Likely Benign	-1.62	Neutral	0.026	Benign	0.015	Benign	4.00	Benign	0.03	Affected			0.1303	0.1187		-3	-2	-8.3	43.03
c.2566A>C	N856H 2D AIThe SynGAP1 missense variant N856H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. 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, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, suggest that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-2.596	Likely Benign	0.100	Likely Benign	Likely Benign										0.059	Likely Benign	-1.26	Neutral	0.990	Probably Damaging	0.923	Probably Damaging	4.10	Benign	0.09	Tolerated			0.1674	0.7495		2	1	0.3	23.04
c.2566A>G	N856D 2D AIThe SynGAP1 missense variant N856D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and consensus analyses indicates that the variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-4.636	Likely Benign	0.195	Likely Benign	Likely Benign										0.091	Likely Benign	-1.25	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.17	Benign	0.61	Tolerated			0.1875	0.4895		2	1	0.0	0.98
c.1021G>T	G341C 2D AIThe SynGAP1 missense variant G341C has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (likely benign). Tools that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; Rosetta remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-6.156	Likely Benign	0.190	Likely Benign	Likely Benign	0.42	Likely Benign	1.2	-0.92	Ambiguous	-0.25	Likely Benign	0.24	Likely Benign	0.501	Likely Pathogenic	-2.40	Neutral	0.997	Probably Damaging	0.870	Possibly Damaging	0.34	Pathogenic	0.01	Affected			0.1285	0.3650		-3	-3	2.9	46.09
c.2560C>G	R854G 2D AIThe SynGAP1 missense variant R854G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all classify the change as benign or likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns a benign score, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750											-2.346	Likely Benign	0.119	Likely Benign	Likely Benign										0.131	Likely Benign	-1.92	Neutral	0.980	Probably Damaging	0.818	Possibly Damaging	4.08	Benign	0.03	Affected			0.3469	0.3764		-3	-2	4.1	-99.14
c.1024T>A	Y342N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y342N has no ClinVar entry (ClinVar status: None) and is not reported in gnomAD (gnomAD ID: None). Prediction tools that assess the variant’s effect are overwhelmingly in agreement that it is deleterious: SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. No tool predicts a benign effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact. Taken together, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250											-9.685	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	1.76	Ambiguous	0.1	2.89	Destabilizing	2.33	Destabilizing	1.02	Destabilizing	0.554	Likely Pathogenic	-6.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.71	Pathogenic	0.03	Affected			0.2189	0.0862		-2	-2	-2.2	-49.07
c.1022G>T	G341V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G341V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, polyPhen‑2 HumVar, and the SGM‑Consensus score (derived from a majority of benign calls among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as uncertain. No evidence from FoldX or premPS is available. Overall, the majority of predictions support a benign classification, and this is consistent with the lack of ClinVar annotation. Therefore, the variant is most likely benign and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-5.371	Likely Benign	0.247	Likely Benign	Likely Benign	0.86	Ambiguous	0.3	-2.24	Stabilizing	-0.69	Ambiguous	-0.50	Ambiguous	0.459	Likely Benign	-2.29	Neutral	0.801	Possibly Damaging	0.192	Benign	0.42	Pathogenic	0.05	Affected			0.1019	0.3649		-1	-3	4.6	42.08
c.2555G>C	G852A 2D AIThe SynGAP1 missense variant G852A is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625											-4.493	Likely Benign	0.068	Likely Benign	Likely Benign										0.142	Likely Benign	-0.35	Neutral	0.393	Benign	0.321	Benign	4.25	Benign	1.00	Tolerated			0.3895	0.4934		1	0	2.2	14.03
c.1022G>C	G341A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G341A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come only from polyPhen‑2 HumDiv and FATHMM. Uncertain results are reported by Rosetta and Foldetta. 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; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains inconclusive. Overall, the preponderance of evidence indicates that G341A is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-3.211	Likely Benign	0.109	Likely Benign	Likely Benign	0.16	Likely Benign	0.4	-1.23	Ambiguous	-0.54	Ambiguous	-0.03	Likely Benign	0.239	Likely Benign	-1.13	Neutral	0.625	Possibly Damaging	0.192	Benign	0.43	Pathogenic	0.15	Tolerated			0.3562	0.3979		1	0	2.2	14.03
c.2555G>T	G852V 2D AIThe SynGAP1 missense variant G852V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G852V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625											-5.629	Likely Benign	0.085	Likely Benign	Likely Benign										0.125	Likely Benign	-1.30	Neutral	0.918	Possibly Damaging	0.697	Possibly Damaging	4.19	Benign	0.02	Affected			0.1205	0.4173		-1	-3	4.6	42.08
c.2557G>A	G853S 2D AIThe SynGAP1 missense variant G853S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that G853S is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-3.878	Likely Benign	0.067	Likely Benign	Likely Benign										0.155	Likely Benign	0.14	Neutral	0.003	Benign	0.008	Benign	4.31	Benign	0.02	Affected			0.2783	0.5206		1	0	-0.4	30.03
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		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625					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			0.0918	0.4323		-3	-2	-4.1	99.14
c.2557G>T	G853C 2D AIThe SynGAP1 G853C missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-7.021	In-Between	0.096	Likely Benign	Likely Benign										0.120	Likely Benign	-1.65	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.00	Affected			0.1292	0.4944		-3	-3	2.9	46.09
c.2558G>A	G853D 2D AIThe SynGAP1 missense variant G853D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of predictors and the high‑accuracy tools points to a benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-5.116	Likely Benign	0.220	Likely Benign	Likely Benign										0.156	Likely Benign	-0.86	Neutral	0.611	Possibly Damaging	0.346	Benign	4.19	Benign	0.00	Affected			0.1745	0.1862		1	-1	-3.1	58.04
c.2558G>C	G853A 2D AIThe SynGAP1 missense variant G853A is predicted to be benign by every evaluated in‑silico tool. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. ClinVar contains no entry for G853A, and the variant is absent from gnomAD. Based on the unanimous benign predictions and lack of contrary evidence, the variant is most likely benign, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-4.440	Likely Benign	0.082	Likely Benign	Likely Benign										0.165	Likely Benign	-0.30	Neutral	0.124	Benign	0.130	Benign	4.20	Benign	0.30	Tolerated			0.3929	0.5527		1	0	2.2	14.03
c.2558G>T	G853V 2D AIThe SynGAP1 missense variant G853V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G853V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-5.688	Likely Benign	0.087	Likely Benign	Likely Benign										0.129	Likely Benign	-1.53	Neutral	0.611	Possibly Damaging	0.502	Possibly Damaging	4.14	Benign	0.01	Affected			0.1188	0.4609		-1	-3	4.6	42.08
c.2560C>A	R854S 2D AIThe SynGAP1 missense variant R854S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the preponderance of evidence points to a benign impact for R854S, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750											-2.875	Likely Benign	0.231	Likely Benign	Likely Benign										0.132	Likely Benign	-1.42	Neutral	0.960	Probably Damaging	0.765	Possibly Damaging	4.14	Benign	0.26	Tolerated			0.3183	0.4687		0	-1	3.7	-69.11
c.2566A>T	N856Y 2D AIThe SynGAP1 missense variant N856Y is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-3.758	Likely Benign	0.189	Likely Benign	Likely Benign										0.152	Likely Benign	-2.45	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	4.07	Benign	0.05	Affected			0.0663	0.6309		-2	-2	2.2	49.07
c.2567A>C	N856T 2D AIThe SynGAP1 missense variant N856T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability result is available, so it does not influence the overall interpretation. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-3.046	Likely Benign	0.096	Likely Benign	Likely Benign										0.037	Likely Benign	-1.63	Neutral	0.818	Possibly Damaging	0.559	Possibly Damaging	4.13	Benign	0.17	Tolerated			0.1493	0.8096		0	0	2.8	-13.00
c.101A>T	Y34F 2D AIThe SynGAP1 missense variant Y34F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-3.275	Likely Benign	0.127	Likely Benign	Likely Benign										0.094	Likely Benign	-0.50	Neutral	0.458	Possibly Damaging	0.481	Possibly Damaging	4.20	Benign	0.00	Affected			0.2604	0.3591		7	3	4.1	-16.00
c.2571C>G	S857R 2D AIThe SynGAP1 missense variant S857R is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.490	Likely Benign	0.718	Likely Pathogenic	Likely Benign										0.132	Likely Benign	-1.09	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	4.07	Benign	0.18	Tolerated			0.1030	0.4112		0	-1	-3.7	69.11
c.1019C>T	A340V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A340V variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) is uncertain and therefore unavailable for interpretation. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.390993	Structured	0.410781	Uncertain	0.558	0.485	0.250											-6.427	Likely Benign	0.174	Likely Benign	Likely Benign	0.69	Ambiguous	0.3	0.32	Likely Benign	0.51	Ambiguous	0.40	Likely Benign	0.102	Likely Benign	-1.81	Neutral	0.801	Possibly Damaging	0.315	Benign	2.09	Pathogenic	0.57	Tolerated			0.1197	0.5780		0	0	2.4	28.05
c.2572A>C	S858R 2D AIThe SynGAP1 missense variant S858R is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a likely benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-3.924	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-1.18	Neutral	0.818	Possibly Damaging	0.899	Possibly Damaging	4.12	Benign	0.02	Affected			0.0996	0.3778		0	-1	-3.7	69.11
c.2572A>G	S858G 2D AIThe SynGAP1 missense variant S858G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumVar indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also predicts benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-2.181	Likely Benign	0.068	Likely Benign	Likely Benign										0.143	Likely Benign	-0.18	Neutral	0.259	Benign	0.786	Possibly Damaging	4.13	Benign	0.11	Tolerated			0.3084	0.5116		1	0	0.4	-30.03
c.2572A>T	S858C 2D AIThe SynGAP1 missense variant S858C is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-6.767	Likely Benign	0.108	Likely Benign	Likely Benign										0.139	Likely Benign	-1.93	Neutral	0.940	Possibly Damaging	0.979	Probably Damaging	4.06	Benign	0.02	Affected			0.1206	0.6155		0	-1	3.3	16.06
c.1019C>G	A340G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A340G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of reliable predictors indicate a benign effect, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.390993	Structured	0.410781	Uncertain	0.558	0.485	0.250											-3.763	Likely Benign	0.099	Likely Benign	Likely Benign	0.66	Ambiguous	0.2	1.44	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	0.044	Likely Benign	-0.34	Neutral	0.267	Benign	0.127	Benign	1.92	Pathogenic	0.42	Tolerated			0.2355	0.4470		1	0	-2.2	-14.03
c.1019C>A	A340E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A340E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a likely pathogenic outcome, while the protein‑folding stability method Foldetta is uncertain. AlphaMissense‑Optimized also yields an uncertain result. Overall, the majority of evidence points toward a pathogenic impact, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.410781	Uncertain	0.558	0.485	0.250											-8.225	Likely Pathogenic	0.803	Likely Pathogenic	Ambiguous	0.63	Ambiguous	0.4	1.55	Ambiguous	1.09	Ambiguous	0.06	Likely Benign	0.138	Likely Benign	-0.33	Neutral	0.625	Possibly Damaging	0.252	Benign	1.91	Pathogenic	0.39	Tolerated			0.1418	0.2160		0	-1	-5.3	58.04
c.2573G>C	S858T 2D AIThe SynGAP1 missense variant S858T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumVar predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that S858T is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-4.960	Likely Benign	0.082	Likely Benign	Likely Benign										0.069	Likely Benign	-0.92	Neutral	0.259	Benign	0.786	Possibly Damaging	4.14	Benign	0.06	Tolerated			0.1660	0.6489		1	1	0.1	14.03
c.2573G>T	S858I 2D AIThe SynGAP1 missense variant S858I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-6.973	Likely Benign	0.234	Likely Benign	Likely Benign										0.125	Likely Benign	-1.53	Neutral	0.818	Possibly Damaging	0.932	Probably Damaging	4.10	Benign	0.01	Affected			0.1016	0.5680		-1	-2	5.3	26.08
c.2574C>A	S858R 2D AIThe SynGAP1 missense variant S858R is reported as “Likely Benign” in ClinVar and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-3.924	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-1.18	Neutral	0.818	Possibly Damaging	0.899	Possibly Damaging	4.12	Benign	0.02	Affected			0.0996	0.3778		0	-1	-3.7	69.11
c.2574C>G	S858R 2D AIThe SynGAP1 missense variant S858R is reported as “Likely Benign” in ClinVar and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-3.924	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-1.18	Neutral	0.818	Possibly Damaging	0.899	Possibly Damaging	4.12	Benign	0.02	Affected			0.0996	0.3778		0	-1	-3.7	69.11
c.2575A>C	S859R 2D AIThe SynGAP1 missense variant S859R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized is uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign (two benign versus one pathogenic vote). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.810	In-Between	0.844	Likely Pathogenic	Ambiguous										0.127	Likely Benign	-1.42	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.00	Benign	0.06	Tolerated			0.0945	0.4061		0	-1	-3.7	69.11
c.2571C>A	S857R 2D AIThe SynGAP1 missense variant S857R is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.490	Likely Benign	0.718	Likely Pathogenic	Likely Benign										0.132	Likely Benign	-1.09	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	4.07	Benign	0.18	Tolerated			0.1030	0.4112		0	-1	-3.7	69.11
c.2570G>T	S857I 2D AIThe SynGAP1 missense variant S857I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S857I, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-7.092	In-Between	0.192	Likely Benign	Likely Benign										0.198	Likely Benign	-0.44	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.05	Affected			0.1070	0.6208		-1	-2	5.3	26.08
c.2567A>T	N856I 2D AIThe SynGAP1 missense variant N856I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv and SIFT predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. Therefore, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-4.360	Likely Benign	0.207	Likely Benign	Likely Benign										0.086	Likely Benign	-2.30	Neutral	0.692	Possibly Damaging	0.202	Benign	4.08	Benign	0.04	Affected			0.0744	0.6453		-2	-3	8.0	-0.94
c.2568C>A	N856K 2D AIThe SynGAP1 missense variant N856K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for N856K, and this conclusion is not in conflict with any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-3.511	Likely Benign	0.429	Ambiguous	Likely Benign										0.079	Likely Benign	-1.51	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.19	Benign	0.26	Tolerated			0.2065	0.6252		1	0	-0.4	14.07
c.2568C>G	N856K 2D AIThe SynGAP1 missense variant N856K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors—AlphaMissense‑Optimized and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for N856K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-3.511	Likely Benign	0.429	Ambiguous	Likely Benign										0.079	Likely Benign	-1.51	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.19	Benign	0.26	Tolerated			0.2065	0.6252		1	0	-0.4	14.07
c.2569A>C	S857R 2D AIThe SynGAP1 missense variant S857R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S857R, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.490	Likely Benign	0.718	Likely Pathogenic	Likely Benign										0.138	Likely Benign	-1.09	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	4.07	Benign	0.18	Tolerated			0.1030	0.4112		0	-1	-3.7	69.11
c.101A>G	Y34C 2D AIThe SynGAP1 missense variant Y34C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized reports Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for Y34C, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-3.730	Likely Benign	0.171	Likely Benign	Likely Benign										0.196	Likely Benign	0.87	Neutral	0.943	Possibly Damaging	0.941	Probably Damaging	4.32	Benign	0.00	Affected			0.3010	0.2719		0	-2	3.8	-60.04
c.101A>C	Y34S 2D AIThe SynGAP1 missense variant Y34S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Y34S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-0.994	Likely Benign	0.237	Likely Benign	Likely Benign										0.178	Likely Benign	-0.60	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	4.19	Benign	0.00	Affected			0.4760	0.2884		-3	-2	0.5	-76.10
c.2569A>G	S857G 2D AIThe SynGAP1 missense variant S857G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S857G, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.316	Likely Benign	0.067	Likely Benign	Likely Benign										0.124	Likely Benign	-0.57	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	4.10	Benign	0.85	Tolerated			0.2963	0.5644		1	0	0.4	-30.03
c.2569A>T	S857C 2D AIThe SynGAP1 missense variant S857C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the majority of predictions and the high‑accuracy consensus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-6.335	Likely Benign	0.109	Likely Benign	Likely Benign										0.146	Likely Benign	-1.28	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.02	Benign	0.08	Tolerated			0.1221	0.6672		0	-1	3.3	16.06
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		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500					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	0.0887	0.4417		4	3	0.3	14.03
c.256G>T	V86F 2D AIThe SynGAP1 missense variant V86F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-5.011	Likely Benign	0.981	Likely Pathogenic	Likely Pathogenic										0.126	Likely Benign	-1.54	Neutral	0.824	Possibly Damaging	0.403	Benign	3.75	Benign	0.00	Affected			0.0755	0.4078		-1	-1	-1.4	48.04
c.2570G>A	S857N 2D AIThe SynGAP1 missense variant S857N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-5.065	Likely Benign	0.137	Likely Benign	Likely Benign										0.128	Likely Benign	0.24	Neutral	0.991	Probably Damaging	0.982	Probably Damaging	4.09	Benign	1.00	Tolerated			0.1515	0.5034		1	1	-2.7	27.03
c.2570G>C	S857T 2D AIThe SynGAP1 missense variant S857T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.840	Likely Benign	0.076	Likely Benign	Likely Benign										0.142	Likely Benign	-0.31	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	4.09	Benign	0.33	Tolerated			0.1645	0.6733		1	1	0.1	14.03
c.2575A>G	S859G 2D AIThe SynGAP1 missense variant S859G is not reported in ClinVar and is absent from gnomAD. In silico predictions cluster into three groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized), pathogenic (polyPhen‑2 HumDiv and HumVar), and uncertain (ESM1b). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S859G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.412	In-Between	0.087	Likely Benign	Likely Benign										0.118	Likely Benign	-0.69	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.00	Benign	0.25	Tolerated			0.2798	0.4988		1	0	0.4	-30.03
c.1008G>T	K336N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for K336N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.2622G>T	Q874H 2D AIThe SynGAP1 missense variant Q874H has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.658	Likely Benign	0.543	Ambiguous	Likely Benign										0.236	Likely Benign	-2.90	Deleterious	0.996	Probably Damaging	0.995	Probably Damaging	2.65	Benign	0.00	Affected			0.1588	0.5088		3	0	0.3	9.01
c.2623G>C	A875P 2D AIThe SynGAP1 missense variant A875P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar all predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Overall, the majority of evidence points to a benign effect for A875P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-3.799	Likely Benign	0.237	Likely Benign	Likely Benign										0.154	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.959	Probably Damaging	2.66	Benign	0.09	Tolerated			0.1750	0.5688		1	-1	-3.4	26.04
c.2623G>T	A875S 2D AIThe SynGAP1 missense variant A875S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that A875S is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-2.719	Likely Benign	0.120	Likely Benign	Likely Benign										0.063	Likely Benign	-1.07	Neutral	0.945	Possibly Damaging	0.767	Possibly Damaging	2.78	Benign	0.08	Tolerated			0.2607	0.6338		1	1	-2.6	16.00
c.2624C>A	A875D 2D AIThe SynGAP1 missense variant A875D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta data are unavailable. Overall, the majority of standard tools (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, but the high‑accuracy predictions are mixed or missing. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-3.268	Likely Benign	0.645	Likely Pathogenic	Likely Benign										0.149	Likely Benign	-2.78	Deleterious	0.992	Probably Damaging	0.913	Probably Damaging	2.68	Benign	0.02	Affected			0.1648	0.2035		0	-2	-5.3	44.01
c.2624C>G	A875G 2D AIThe SynGAP1 missense variant A875G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-2.904	Likely Benign	0.111	Likely Benign	Likely Benign										0.078	Likely Benign	-1.22	Neutral	0.022	Benign	0.048	Benign	2.68	Benign	0.04	Affected			0.2308	0.5046		1	0	-2.2	-14.03
c.2624C>T	A875V 2D AIThe SynGAP1 missense variant A875V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-4.946	Likely Benign	0.255	Likely Benign	Likely Benign										0.116	Likely Benign	-1.17	Neutral	0.991	Probably Damaging	0.904	Possibly Damaging	2.74	Benign	1.00	Tolerated			0.1099	0.6605		0	0	2.4	28.05
c.1003C>G	R335G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and SIFT, whereas those that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, more tools predict pathogenicity than benignity, and the high‑accuracy consensus also leans pathogenic. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-11.860	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous	1.01	Ambiguous	0.1	0.44	Likely Benign	0.73	Ambiguous	0.20	Likely Benign	0.194	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.01	Pathogenic	0.10	Tolerated			0.3000	0.3554		-3	-2	4.1	-99.14
c.2626T>A	S876T 2D AIThe SynGAP1 missense variant S876T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250											-5.158	Likely Benign	0.183	Likely Benign	Likely Benign										0.121	Likely Benign	-1.91	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.60	Benign	0.11	Tolerated			0.1380	0.6790		1	1	0.1	14.03
c.2626T>C	S876P 2D AIThe SynGAP1 missense variant S876P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that S876P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250											-5.002	Likely Benign	0.229	Likely Benign	Likely Benign										0.171	Likely Benign	-2.04	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.56	Benign	0.35	Tolerated			0.1979	0.6928		1	-1	-0.8	10.04
c.2626T>G	S876A 2D AIThe SynGAP1 missense variant S876A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250											-4.228	Likely Benign	0.154	Likely Benign	Likely Benign										0.091	Likely Benign	-1.43	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.63	Benign	0.54	Tolerated			0.4495	0.5889		1	1	2.6	-16.00
c.1003C>A	R335S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX or Rosetta alone is available. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic, which is consistent with the absence of ClinVar reporting and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-9.286	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.68	Ambiguous	0.1	0.72	Ambiguous	0.70	Ambiguous	0.14	Likely Benign	0.184	Likely Benign	-3.30	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.89	Pathogenic	0.11	Tolerated			0.2598	0.4005		0	-1	3.7	-69.11
c.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.			0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250					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	0.1268	0.6053		-2	-3	4.6	26.08
c.2622G>C	Q874H 2D AIThe SynGAP1 missense variant Q874H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the balance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.658	Likely Benign	0.543	Ambiguous	Likely Benign										0.236	Likely Benign	-2.90	Deleterious	0.996	Probably Damaging	0.995	Probably Damaging	2.65	Benign	0.00	Affected			0.1588	0.5088		3	0	0.3	9.01
c.2621A>T	Q874L 2D AIThe SynGAP1 missense variant Q874L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-6.084	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.199	Likely Benign	-3.39	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.00	Affected			0.0828	0.6595		-2	-2	7.3	-14.97
c.1008G>C	K336N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus also predicts likely pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. No prediction or stability result is missing. Overall, the majority of tools and the high‑accuracy methods lean toward pathogenicity, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status because ClinVar has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.2618G>T	S873I 2D AIThe SynGAP1 missense variant S873I has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. High‑accuracy assessment therefore points to a Likely Pathogenic status from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Overall, the preponderance of evidence suggests the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-9.412	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.305	Likely Benign	-3.44	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.02	Affected			0.1012	0.5560		-1	-2	5.3	26.08
c.2619C>A	S873R 2D AIThe SynGAP1 missense variant S873R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions, with a pathogenic high‑accuracy tool) suggests the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-5.856	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.06	Tolerated	3.77	5	0.0970	0.3667		0	-1	-3.7	69.11
c.1007A>T	K336M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS) and pathogenic predictions (SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” Stability‑based assessments are inconclusive: Foldetta is uncertain, and Rosetta is also uncertain. High‑accuracy tools specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms pathogenic, while Foldetta remains uncertain. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-15.395	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.1	0.82	Ambiguous	0.58	Ambiguous	-0.23	Likely Benign	0.301	Likely Benign	-5.07	Deleterious	0.989	Probably Damaging	0.832	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.1185	0.4760		0	-1	5.8	3.02
c.2620C>A	Q874K 2D AIThe SynGAP1 missense variant Q874K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-6.379	Likely Benign	0.604	Likely Pathogenic	Likely Benign										0.169	Likely Benign	-2.35	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.73	Benign	0.00	Affected			0.2008	0.4893		1	1	-0.4	0.04
c.2620C>G	Q874E 2D AIThe SynGAP1 missense variant Q874E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for Q874E, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.576	Likely Benign	0.197	Likely Benign	Likely Benign										0.193	Likely Benign	-1.95	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.73	Benign	0.00	Affected			0.1489	0.3577		2	2	0.0	0.98
c.1007A>C	K336T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy assessment shows AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for K336T, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-13.468	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.33	Likely Benign	0.1	-0.08	Likely Benign	0.13	Likely Benign	0.15	Likely Benign	0.212	Likely Benign	-4.94	Deleterious	0.891	Possibly Damaging	0.315	Benign	1.58	Pathogenic	0.01	Affected			0.2014	0.4048		0	-1	3.2	-27.07
c.1006A>G	K336E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for K336E, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-16.091	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	-0.28	Likely Benign	0.0	0.19	Likely Benign	-0.05	Likely Benign	0.35	Likely Benign	0.236	Likely Benign	-3.43	Deleterious	0.625	Possibly Damaging	0.192	Benign	1.60	Pathogenic	0.01	Affected			0.4003	0.1082		0	1	0.4	0.94
c.1006A>C	K336Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K336Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. Because the predictions are evenly split and the high‑accuracy methods give conflicting results, the variant is best classified as of uncertain significance. This assessment does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-12.876	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous	0.02	Likely Benign	0.0	-0.17	Likely Benign	-0.08	Likely Benign	0.18	Likely Benign	0.211	Likely Benign	-3.30	Deleterious	0.801	Possibly Damaging	0.252	Benign	1.58	Pathogenic	0.02	Affected			0.4698	0.1514		1	1	0.4	-0.04
c.1004G>T	R335L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335L is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX are uncertain and are treated as unavailable for pathogenicity inference. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-13.226	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	-0.19	Likely Benign	0.16	Likely Benign	0.40	Likely Benign	0.196	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.73	Pathogenic	0.04	Affected			0.1382	0.4753		-3	-2	8.3	-43.03
c.2621A>G	Q874R 2D AIThe SynGAP1 missense variant Q874R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts a benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.834	Likely Benign	0.527	Ambiguous	Likely Benign										0.200	Likely Benign	-2.33	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.00	Affected			0.1619	0.2924		1	1	-1.0	28.06
c.1004G>C	R335P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and SIFT, whereas pathogenic predictions are reported by FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments give a more focused view: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. Taken together, the majority of evidence points to a pathogenic impact for R335P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-13.952	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	3.23	Destabilizing	0.8	5.73	Destabilizing	4.48	Destabilizing	0.43	Likely Benign	0.250	Likely Benign	-4.22	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.69	Pathogenic	0.09	Tolerated			0.1866	0.4497		0	-2	2.9	-59.07
c.2629C>A	L877M 2D AIThe SynGAP1 missense variant L877M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the two polyPhen‑2 scores (HumDiv and HumVar) predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-6.266	Likely Benign	0.134	Likely Benign	Likely Benign										0.068	Likely Benign	-0.55	Neutral	0.922	Possibly Damaging	0.776	Possibly Damaging	2.58	Benign	0.15	Tolerated			0.0813	0.3532		4	2	-1.9	18.03
c.1002G>T	K334N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” Separately, the high‑accuracy AlphaMissense‑Optimized tool predicts pathogenicity, the SGM‑Consensus also predicts pathogenicity, while the Foldetta stability assessment predicts a benign effect. Overall, the majority of predictions (8 pathogenic vs. 5 benign) and the high‑accuracy consensus suggest that K334N is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-9.581	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.1	-0.25	Likely Benign	-0.05	Likely Benign	0.18	Likely Benign	0.249	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.77	Pathogenic	0.02	Affected			0.3716	0.0958		1	0	0.4	-14.07
c.2629C>G	L877V 2D AIThe SynGAP1 missense variant L877V is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-5.063	Likely Benign	0.097	Likely Benign	Likely Benign										0.022	Likely Benign	-0.10	Neutral	0.232	Benign	0.109	Benign	2.71	Benign	0.26	Tolerated			0.1726	0.3178		2	1	0.4	-14.03
c.2633C>T	T878I 2D AIThe SynGAP1 missense variant T878I is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect. **Benign:** REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized. **Pathogenic:** polyPhen‑2 HumDiv, SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the computational evidence overwhelmingly points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.628767	Binding	0.288	0.878	0.250											-6.247	Likely Benign	0.459	Ambiguous	Likely Benign										0.055	Likely Benign	-1.99	Neutral	0.761	Possibly Damaging	0.398	Benign	2.63	Benign	0.00	Affected			0.0980	0.6502		0	-1	5.2	12.05
c.1001A>C	K334T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334T is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-8.313	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.3	0.21	Likely Benign	0.50	Ambiguous	0.17	Likely Benign	0.320	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.02	Affected			0.2062	0.2978		0	-1	3.2	-27.07
c.2635G>C	A879P 2D AIThe SynGAP1 missense variant A879P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that A879P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250											-4.317	Likely Benign	0.114	Likely Benign	Likely Benign										0.151	Likely Benign	-1.16	Neutral	0.986	Probably Damaging	0.825	Possibly Damaging	2.61	Benign	0.23	Tolerated			0.1713	0.5004		1	-1	-3.4	26.04
c.2635G>T	A879S 2D AIThe SynGAP1 missense variant A879S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250											-3.406	Likely Benign	0.086	Likely Benign	Likely Benign										0.091	Likely Benign	-0.26	Neutral	0.580	Possibly Damaging	0.324	Benign	2.68	Benign	0.44	Tolerated			0.2469	0.5266		1	1	-2.6	16.00
c.2635_2636delinsAA	A879K 2D AIThe SynGAP1 missense variant A879K is listed in ClinVar (ID 575856.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this consensus aligns with the ClinVar designation, with no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250					Likely Benign		1				-5.877	Likely Benign	0.757	Likely Pathogenic	Likely Benign												-0.71	Neutral	0.969	Probably Damaging	0.593	Possibly Damaging	2.69	Benign	0.21	Tolerated	3.77	5	0.0930	0.2569		-1	-1	-5.7	57.10
c.1000A>G	K334E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-12.770	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.2	-0.07	Likely Benign	0.12	Likely Benign	0.42	Likely Benign	0.372	Likely Benign	-3.67	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.74	Pathogenic	0.02	Affected			0.3929	0.0882		0	1	0.4	0.94
c.1000A>C	K334Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, and premPS. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. With seven tools favoring pathogenicity versus five favoring benign, the overall prediction leans toward pathogenic. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-8.185	Likely Pathogenic	0.810	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	0.10	Likely Benign	0.09	Likely Benign	0.46	Likely Benign	0.357	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.74	Pathogenic	0.03	Affected			0.4519	0.1062		1	1	0.4	-0.04
c.2636C>T	A879V 2D AIThe SynGAP1 missense variant A879V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250											-6.177	Likely Benign	0.152	Likely Benign	Likely Benign										0.065	Likely Benign	-1.46	Neutral	0.872	Possibly Damaging	0.580	Possibly Damaging	2.64	Benign	0.19	Tolerated			0.1003	0.6293		0	0	2.4	28.05
c.2638G>A	A880T 2D AIThe SynGAP1 missense variant A880T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.621441	Binding	0.309	0.874	0.250											-4.594	Likely Benign	0.083	Likely Benign	Likely Benign										0.097	Likely Benign	-0.75	Neutral	0.761	Possibly Damaging	0.399	Benign	2.61	Benign	0.29	Tolerated			0.1229	0.6396		1	0	-2.5	30.03
c.2638G>C	A880P 2D AIThe SynGAP1 missense variant A880P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.621441	Binding	0.309	0.874	0.250											-3.671	Likely Benign	0.105	Likely Benign	Likely Benign										0.098	Likely Benign	-0.55	Neutral	0.971	Probably Damaging	0.693	Possibly Damaging	2.61	Benign	0.11	Tolerated			0.1744	0.4106		1	-1	-3.4	26.04