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.1036G>A	V346M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V346M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FoldX, whereas the majority of other in silico methods (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, PROVEAN, AlphaMissense‑Optimized, and the SGM‑Consensus score) indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-10.218	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	2.52	Destabilizing	1.41	Ambiguous	0.67	Ambiguous	0.367	Likely Benign	-2.72	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.05	Affected			0.1050	0.4749		2	1	-2.3	32.06
c.1042G>A	V348M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V348M is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that report a clear outcome fall into two groups: benign calls come from REVEL, Foldetta, PROVEAN, and AlphaMissense‑Optimized; pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, ESM1b) give uncertain results, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to no majority. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus is not available. With four benign and four pathogenic predictions, the evidence is evenly split, providing no definitive direction. Therefore, the variant is not clearly benign or pathogenic based on current predictions, and this lack of consensus does not contradict its ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000					Uncertain		1				-7.076	In-Between	0.546	Ambiguous	Likely Benign	-1.19	Ambiguous	0.1	0.72	Ambiguous	-0.24	Likely Benign	0.76	Ambiguous	0.191	Likely Benign	-1.62	Neutral	0.966	Probably Damaging	0.564	Possibly Damaging	1.58	Pathogenic	0.03	Affected	3.37	25	0.0903	0.4748		2	1	-2.3	32.06	253.8	-47.4	-0.3	0.1	0.2	0.1						X		Potentially Benign	The iso-propyl side chain of Val348, located in an anti-parallel β sheet strand (res. Gly341-Pro349), packs against multiple hydrophobic C2 domain residues (e.g., Leu353, Leu323, Leu402). In the variant simulations, the thioether side chain of Met348 can form similar interactions as valine due to its comparable hydrophobic profile. In fact, the thioether group of methionine can even stack favorably with the phenol ring of Tyr363 in the anti-parallel β sheet strand (res. Ala399-Ile411). Overall, the residue swap does not appear to cause negative effects on the protein structure based on the simulations.
c.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.1198G>A	V400M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V400M is reported in gnomAD (ID 6‑33438103‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, 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. In contrast, only three tools—polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default—predict pathogenicity. 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 FoldX or premPS is available. Overall, the preponderance of predictions, including the high‑accuracy methods, supports a benign classification, which is consistent with the absence of a ClinVar pathogenic report. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.398279	Structured	0.415488	Uncertain	0.951	0.451	0.000								6-33438103-G-A	3	1.86e-6	-5.438	Likely Benign	0.573	Likely Pathogenic	Likely Benign	-1.12	Ambiguous	0.1	-0.16	Likely Benign	-0.64	Ambiguous	0.55	Ambiguous	0.443	Likely Benign	-1.44	Neutral	0.868	Possibly Damaging	0.289	Benign	5.26	Benign	0.01	Affected	3.38	27	0.0851	0.4643		1	2	-2.3	32.06
c.1660G>A	V554M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V554M is not reported in ClinVar but is present in gnomAD (ID 6‑33438903‑G‑A). Functional prediction tools show a split opinion: benign calls come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessment focuses on AlphaMissense‑Optimized, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. AlphaMissense‑Optimized predicts benign, the SGM Consensus is a tie and thus unavailable, and Foldetta is uncertain, so it is treated as unavailable. Overall, the available evidence leans toward a benign effect, and this does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000								6-33438903-G-A	1	6.20e-7	-8.118	Likely Pathogenic	0.671	Likely Pathogenic	Likely Benign	-1.11	Ambiguous	0.0	-0.20	Likely Benign	-0.66	Ambiguous	0.73	Ambiguous	0.217	Likely Benign	-2.26	Neutral	0.994	Probably Damaging	0.867	Possibly Damaging	3.22	Benign	0.00	Affected	3.37	35	0.0743	0.2810		1	2	-2.3	32.06
c.1678G>A	V560M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V560M missense variant is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6-33440730-G-A). Functional prediction tools that agree on a benign effect include FoldX, Foldetta, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Uncertain predictions come from Rosetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of high‑confidence tools predict a benign impact, with only one consensus pathogenic prediction. Therefore, the variant is most likely benign based on current computational evidence, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.021381	Structured	0.013872	Uncertain	0.853	0.204	0.000					Uncertain		2	6-33440730-G-A	15	9.50e-6	-9.598	Likely Pathogenic	0.517	Ambiguous	Likely Benign	-0.33	Likely Benign	0.1	0.88	Ambiguous	0.28	Likely Benign	0.72	Ambiguous	0.520	Likely Pathogenic	-2.42	Neutral	0.999	Probably Damaging	0.863	Possibly Damaging	-1.25	Pathogenic	0.14	Tolerated	3.37	35	0.1161	0.3980		2	1	-2.3	32.06	234.9	-52.6	0.0	0.0	-0.1	0.1						X		Potentially Benign	Val560 is located on the surface at the end of an α-helix (res. Ala533-Val560). The iso-propyl group of Val560 favorably packs against Asp508 of the opposing α-helix (res. Gln503-Glu519). However, in the variant simulations, the bulkier thioether side chain of Met560 does not form equally favorable inter-helix interactions. Regardless, no negative structural effects are observed during the simulations.
c.1702G>A	V568M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568M is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, whereas the remaining tools—REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the majority of evidence pointing to pathogenicity and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000											-10.361	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.06	Likely Benign	0.3	2.71	Destabilizing	1.39	Ambiguous	0.66	Ambiguous	0.811	Likely Pathogenic	-2.79	Deleterious	0.997	Probably Damaging	0.924	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.0697	0.3124		2	1	-2.3	32.06
c.2095G>A	V699M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V699M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441354‑G‑A). Across in silico predictors, benign calls are made by REVEL, Rosetta, Foldetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Predictions that are inconclusive (FoldX, premPS, AlphaMissense‑Default) are noted but not used as 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 (combining FoldX‑MD and Rosetta outputs) reports benign stability. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the ClinVar uncertain status but provides a stronger leaning toward benignity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000					Uncertain		2	6-33441354-G-A	8	4.96e-6	-8.869	Likely Pathogenic	0.484	Ambiguous	Likely Benign	-0.58	Ambiguous	0.1	0.29	Likely Benign	-0.15	Likely Benign	0.96	Ambiguous	0.276	Likely Benign	-2.18	Neutral	0.994	Probably Damaging	0.806	Possibly Damaging	3.37	Benign	0.03	Affected	3.47	10	0.0734	0.3071		2	1	-2.3	32.06	257.8	-47.2	0.0	0.0	0.9	0.1						X		Potentially Benign	The isopropyl side chain of Val699, located on an α-helix (res. Leu685-Gln702), packs against hydrophobic residues (e.g., Leu703, Leu696, Leu435, Leu439) in the inter-helix space. In the variant simulations, the thioether side chain of Met699 has similar physicochemical properties to Val699 in the WT, and thus, it is able to maintain similar interactions. Consequently, the mutation causes no apparent changes in the structure.
c.2236G>A	V746M 2D AIThe SynGAP1 missense variant V746M 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 in the dataset 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, was not available for this variant. Overall, the consensus of available predictions strongly suggests that V746M is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.808535	Disordered	0.576597	Binding	0.336	0.867	0.875											-4.194	Likely Benign	0.087	Likely Benign	Likely Benign										0.010	Likely Benign	-0.58	Neutral	0.065	Benign	0.037	Benign	2.79	Benign	0.60	Tolerated			0.0756	0.4576		2	1	-2.3	32.06
c.2521G>A	V841M 2D AISynGAP1 variant V841M is listed in ClinVar with an uncertain significance and is present in gnomAD (6-33443073-G-A). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The ESM1b score is inconclusive. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta stability analysis is unavailable. Taken together, the majority of evidence, including the high‑accuracy tools, points to a benign effect for V841M. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125					Uncertain		1	6-33443073-G-A	3	1.86e-6	-7.000	In-Between	0.651	Likely Pathogenic	Likely Benign										0.119	Likely Benign	-0.74	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.54	Benign	0.02	Affected	3.77	5	0.0707	0.3937		1	2	-2.3	32.06
c.262G>A	V88M 2D AISynGAP1 missense variant V88M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. AlphaMissense‑Optimized alone predicts Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a benign effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-5.851	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.103	Likely Benign	-0.91	Neutral	0.975	Probably Damaging	0.171	Benign	3.67	Benign	0.00	Affected			0.1293	0.4463		2	1	-2.3	32.06
c.268G>A	V90M 2D AIThe SynGAP1 missense variant V90M is listed in gnomAD (6‑33425876‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500								6-33425876-G-A	1	6.20e-7	-5.017	Likely Benign	0.463	Ambiguous	Likely Benign										0.053	Likely Benign	-0.15	Neutral	0.872	Possibly Damaging	0.162	Benign	3.98	Benign	0.00	Affected	4.32	1	0.1221	0.4393		1	2	-2.3	32.06
c.3463G>A	V1155M 2D AISynGAP1 missense variant V1155M is not reported in ClinVar and is present in gnomAD (ID 6‑33444498‑G‑A). Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, with no conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500								6-33444498-G-A	1	6.20e-7	-3.818	Likely Benign	0.915	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-1.19	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.57	Benign	0.02	Affected	3.77	5	0.0779	0.4079		1	2	-2.3	32.06
c.3511_3512delinsTG	A1171C 2D AIThe SynGAP1 missense variant A1171C (ClinVar ID 1723483.0) is listed as “Uncertain” in ClinVar and is not present in gnomAD. Prediction tools that converge on a benign outcome include PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which report a benign or neutral effect. In contrast, PolyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign,” reinforcing the benign signal. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote) as benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500					Uncertain		1				-5.363	Likely Benign	0.496	Ambiguous	Likely Benign												-1.16	Neutral	0.978	Probably Damaging	0.825	Possibly Damaging	5.32	Benign	0.02	Affected	4.32	4	0.1102	0.4921		-2	0	0.7	32.06
c.3583G>A	V1195M 2D AIThe SynGAP1 V1195M missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools split evenly: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is “Uncertain,” SGM‑Consensus (majority vote) is benign, and Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the SGM‑Consensus and the balance of individual predictors—leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-3.564	Likely Benign	0.944	Likely Pathogenic	Ambiguous										0.409	Likely Benign	-1.01	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	5.46	Benign	0.04	Affected			0.0589	0.3421		2	1	-2.3	32.06
c.3805G>A	V1269M 2D AIThe SynGAP1 missense variant V1269M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for V1269M, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.743	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0582	0.3676		2	1	-2.3	32.06
c.3925G>A	V1309M 2D AIThe SynGAP1 missense variant V1309M is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6-33451799-G-A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign impact for V1309M, and this conclusion does not contradict ClinVar status, which currently has no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.948596	Binding	0.402	0.907	0.750								6-33451799-G-A	1	6.20e-7	-4.653	Likely Benign	0.183	Likely Benign	Likely Benign										0.072	Likely Benign	0.18	Neutral	0.651	Possibly Damaging	0.346	Benign	2.44	Pathogenic	0.04	Affected	3.77	5	0.0820	0.4116		1	2	-2.3	32.06
c.625G>A	V209M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V209M 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 FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125											-8.112	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.70	Ambiguous	0.4	0.77	Ambiguous	0.74	Ambiguous	0.78	Ambiguous	0.115	Likely Benign	-1.48	Neutral	0.995	Probably Damaging	0.880	Possibly Damaging	3.68	Benign	0.02	Affected			0.0669	0.3982		2	1	-2.3	32.06
c.787G>A	V263M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V263M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. 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) reports Benign. No conflicting evidence is present. **Based on the aggregate 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	0.268042	Structured	0.356141	Uncertain	0.918	0.257	0.000											-5.956	Likely Benign	0.218	Likely Benign	Likely Benign	0.20	Likely Benign	0.1	-0.24	Likely Benign	-0.02	Likely Benign	0.43	Likely Benign	0.444	Likely Benign	-0.95	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	5.84	Benign	0.03	Affected			0.0665	0.3545		2	1	-2.3	32.06
c.1231A>T	I411F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-13.377	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	5.71	Destabilizing	0.1	4.53	Destabilizing	5.12	Destabilizing	0.73	Ambiguous	0.503	Likely Pathogenic	-3.69	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.30	Benign	0.00	Affected			0.0538	0.2853		1	0	-1.7	34.02
c.1236G>C	L412F 2D AIThe SynGAP1 missense variant L412F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas the majority of tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Taken together, the consensus of the majority of evidence points to a pathogenic effect for L412F, 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	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-8.710	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	7.00	Destabilizing	3.5	3.61	Destabilizing	5.31	Destabilizing	0.48	Likely Benign	0.286	Likely Benign	-3.69	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.27	Benign	0.04	Affected			0.0602	0.2891		2	0	-1.0	34.02
c.1236G>T	L412F 2D AIThe SynGAP1 missense variant L412F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas the majority of tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Taken together, the consensus of the majority of evidence points to a pathogenic effect for L412F, 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	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-8.710	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	7.00	Destabilizing	3.5	3.61	Destabilizing	5.31	Destabilizing	0.48	Likely Benign	0.283	Likely Benign	-3.69	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.27	Benign	0.04	Affected			0.0602	0.2891		2	0	-1.0	34.02
c.1305G>C	L435F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, providing no definitive evidence for either outcome. Given the preponderance of pathogenic predictions and the lack of any ClinVar annotation to contradict this assessment, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-11.871	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	0.95	Ambiguous	0.73	Ambiguous	0.69	Ambiguous	0.222	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.26	Benign	0.01	Affected			0.0587	0.2723		2	0	-1.0	34.02
c.1305G>T	L435F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (Likely Pathogenic). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, providing no definitive evidence for either outcome. Given the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-11.871	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	0.95	Ambiguous	0.73	Ambiguous	0.69	Ambiguous	0.222	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.26	Benign	0.01	Affected			0.0587	0.2723		2	0	-1.0	34.02
c.1360A>T	I454F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. premPS is uncertain and does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the absence of benign evidence, the variant is most likely pathogenic, with no ClinVar status to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-12.468	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	4.15	Destabilizing	0.7	2.96	Destabilizing	3.56	Destabilizing	0.70	Ambiguous	0.464	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.33	Benign	0.00	Affected			0.0422	0.2560		1	0	-1.7	34.02
c.1393C>T	L465F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465F is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and Rosetta, whereas the majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools (Foldetta and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also pathogenic, and Foldetta remains uncertain. Overall, the consensus of high‑confidence predictors points to a pathogenic effect for L465F. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-12.626	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.7	0.05	Likely Benign	1.58	Ambiguous	0.52	Ambiguous	0.432	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.0771	0.2759		2	0	-1.0	34.02
c.1444C>T	L482F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX and premPS, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as Uncertain, SGM Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L482F. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.257	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.48	Likely Benign	0.0	1.09	Ambiguous	0.79	Ambiguous	0.43	Likely Benign	0.724	Likely Pathogenic	-3.95	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	-1.22	Pathogenic	0.01	Affected			0.0457	0.1814		2	0	-1.0	34.02
c.1465C>T	L489F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489F is listed in ClinVar with an uncertain significance (ClinVar ID 522018.0) and is present in the gnomAD database (gnomAD ID 6‑33438497‑C‑T). In silico prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while no tool predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No prediction or folding‑stability result is missing or ambiguous. **Thus, the variant is most likely pathogenic based on the collective predictions, and this does not contradict the ClinVar uncertain status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125					Uncertain		2	6-33438497-C-T	1	6.20e-7	-12.066	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.5	1.14	Ambiguous	1.43	Ambiguous	0.56	Ambiguous	0.724	Likely Pathogenic	-3.76	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.51	Pathogenic	0.01	Affected	3.37	35	0.0791	0.3729		2	0	-1.0	34.02	246.4	-17.8	0.0	0.0	0.6	0.1						X		Potentially Benign	The iso-butyl side chain of Leu489, located in the α-helix (res. Leu489-Glu519) within an inter-helix space of four helices (res. Ala461-Phe476, res. Val441-Ser457, and res. Met414-Glu436), packs with hydrophobic residues (e.g., Cys432, Ala448, Lys444, Ala493, Val447, Met468) in the inter-helix space. In the variant simulations, the phenyl ring of the Phe489 side chain can also pack favorably in the hydrophobic region. However, due to the size difference, the aromatic side chain of Phe489 tends to reposition to escape the tight region to accommodate the larger side chain, stacking with Lys444. Although no apparent negative changes are observed during the variant simulation, the size difference between the swapped residues could affect the protein folding process.
c.148A>T	I50F 2D AIThe SynGAP1 missense variant I50F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for I50F, 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		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-5.631	Likely Benign	0.681	Likely Pathogenic	Likely Benign										0.100	Likely Benign	-1.27	Neutral	0.334	Benign	0.074	Benign	3.75	Benign	0.00	Affected			0.0483	0.2560		1	0	-1.7	34.02
c.1501A>T	I501F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I501F missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain (a stability method that integrates FoldX‑MD and Rosetta outputs). No predictions are missing or inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-12.113	Likely Pathogenic	0.664	Likely Pathogenic	Likely Benign	3.06	Destabilizing	0.1	0.26	Likely Benign	1.66	Ambiguous	0.71	Ambiguous	0.385	Likely Benign	-3.88	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.40	Benign	0.03	Affected			0.0574	0.1594		1	0	-1.7	34.02
c.1516C>T	L506F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; premPS and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000					Uncertain		1				-11.262	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	4.92	Destabilizing	0.8	5.76	Destabilizing	5.34	Destabilizing	0.91	Ambiguous	0.464	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.01	Affected	3.37	35	0.0566	0.1471		0	2	-1.0	34.02
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.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.1540A>T	I514F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report it as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, classifies the variant as pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.221408	Uncertain	0.948	0.266	0.000					Uncertain		1				-13.383	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.35	Destabilizing	0.3	3.74	Destabilizing	3.05	Destabilizing	0.93	Ambiguous	0.601	Likely Pathogenic	-3.98	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	2.89	Benign	0.00	Affected	3.37	35	0.0574	0.1629		0	1	-1.7	34.02
c.1585A>T	I529F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I529F is not reported in ClinVar and is present in gnomAD (variant ID 6‑33438828‑A‑T). Consensus from most in‑silico predictors classifies the change as benign: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic effect. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus is Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. Overall, the preponderance of evidence indicates that I529F 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	GAP	0.318242	Structured	0.019545	Uncertain	0.901	0.403	0.000								6-33438828-A-T	4	2.48e-6	-5.669	Likely Benign	0.235	Likely Benign	Likely Benign	-0.21	Likely Benign	0.0	0.06	Likely Benign	-0.08	Likely Benign	0.06	Likely Benign	0.320	Likely Benign	-0.97	Neutral	0.266	Benign	0.054	Benign	-1.30	Pathogenic	0.23	Tolerated	3.37	35	0.0522	0.2713		0	1	-1.7	34.02
c.1608G>C	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.724	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.1608G>T	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.722	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.1647G>C	L549F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L549F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include Rosetta, premPS, and SIFT, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000					Uncertain		1				-11.634	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.3	0.27	Likely Benign	0.54	Ambiguous	0.49	Likely Benign	0.514	Likely Pathogenic	-3.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.29	Pathogenic	0.14	Tolerated			0.0724	0.1859		2	0	-1.0	34.02
c.1647G>T	L549F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L549F is not reported in ClinVar and is absent from gnomAD. Benign predictions come from Rosetta, premPS, and SIFT, whereas pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score indicates likely pathogenic, while FoldX and Foldetta are uncertain. High‑accuracy tools specifically: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000											-11.634	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.3	0.27	Likely Benign	0.54	Ambiguous	0.49	Likely Benign	0.514	Likely Pathogenic	-3.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.29	Pathogenic	0.14	Tolerated			0.0724	0.1859		2	0	-1.0	34.02
c.169C>T	L57F 2D AIThe SynGAP1 missense variant L57F (ClinVar ID 1973575.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion aligns with the ClinVar “Uncertain” status, as it does not contradict the current classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000					Uncertain		2				-5.096	Likely Benign	0.459	Ambiguous	Likely Benign										0.051	Likely Benign	-0.78	Neutral	0.824	Possibly Damaging	0.879	Possibly Damaging	3.96	Benign	0.00	Affected	4.32	1	0.0679	0.3355		2	0	-1.0	34.02
c.1750A>T	I584F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I584F missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta, whereas the remaining pathogenic‑predicating tools—REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently classify the variant as deleterious. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” while AlphaMissense‑Optimized and Foldetta yield uncertain results and are therefore not used as evidence. No other folding‑stability methods provide definitive support. 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	GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000											-13.582	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	3.20	Destabilizing	0.2	0.28	Likely Benign	1.74	Ambiguous	0.66	Ambiguous	0.618	Likely Pathogenic	-3.47	Deleterious	0.980	Probably Damaging	0.808	Possibly Damaging	-1.26	Pathogenic	0.04	Affected			0.0641	0.2150		1	0	-1.7	34.02
c.1762C>T	L588F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588F is reported in gnomAD (variant ID 6‑33440814‑C‑T) but has no ClinVar entry. Across the available in‑silico predictors, every tool examined classifies the substitution as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic or likely pathogenic scores. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Because every available prediction converges on a deleterious effect and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000								6-33440814-C-T			-14.050	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.2	2.55	Destabilizing	2.73	Destabilizing	1.12	Destabilizing	0.736	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.38	Pathogenic	0.04	Affected	3.38	34	0.0816	0.2007		0	2	-1.0	34.02
c.1765A>T	I589F 2D AIThe SynGAP1 missense variant I589F is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a pathogenic impact. All available predictions are concordant and supportive. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018415	Structured	0.084536	Uncertain	0.927	0.214	0.000											-15.300	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	7.38	Destabilizing	3.4	2.05	Destabilizing	4.72	Destabilizing	1.04	Destabilizing	0.905	Likely Pathogenic	-3.98	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.98	Pathogenic	0.00	Affected			0.0888	0.2574		1	0	-1.7	34.02
c.1777C>T	L593F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L593F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive—FoldX, Foldetta, premPS, and AlphaMissense‑Optimized—are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-12.723	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	1.46	Ambiguous	0.4	0.24	Likely Benign	0.85	Ambiguous	0.62	Ambiguous	0.304	Likely Benign	-3.78	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.95	Benign	0.01	Affected			0.0884	0.2631		2	0	-1.0	34.02
c.1792C>T	L598F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L598F is not reported in ClinVar and is absent from gnomAD. Computational predictors show mixed results: benign calls come from REVEL, Rosetta, premPS, SIFT, and FATHMM; pathogenic calls come from SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized returned uncertain results, which are treated as unavailable evidence. High‑accuracy tools give a split view: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the balance of evidence leans toward pathogenicity, with six pathogenic versus five benign predictions and no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-10.649	Likely Pathogenic	0.820	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.7	-0.24	Likely Benign	0.44	Likely Benign	0.47	Likely Benign	0.283	Likely Benign	-3.91	Deleterious	0.999	Probably Damaging	0.946	Probably Damaging	3.62	Benign	0.22	Tolerated			0.0630	0.1414		2	0	-1.0	34.02
c.1804A>T	I602F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I602F missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-13.974	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	2.47	Destabilizing	1.1	-0.61	Ambiguous	0.93	Ambiguous	0.87	Ambiguous	0.822	Likely Pathogenic	-3.98	Deleterious	0.999	Probably Damaging	0.937	Probably Damaging	-1.82	Pathogenic	0.00	Affected			0.0708	0.2343		1	0	-1.7	34.02
c.1819C>T	L607F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607F is catalogued in gnomAD (6‑33440871‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all report pathogenic or likely pathogenic. Only FoldX predicts a benign outcome, while Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L607F, and this conclusion is not contradicted by ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000								6-33440871-C-T	1	6.19e-7	-13.654	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	1.20	Ambiguous	0.72	Ambiguous	0.61	Ambiguous	0.758	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected	3.37	35	0.0872	0.2816		0	2	-1.0	34.02
c.1828C>T	L610F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610F 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, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—all of which classify the variant as pathogenic. No tools predict a benign outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the consensus of these 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	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-13.244	Likely Pathogenic	0.808	Likely Pathogenic	Ambiguous	6.24	Destabilizing	1.1	3.40	Destabilizing	4.82	Destabilizing	0.68	Ambiguous	0.782	Likely Pathogenic	-3.92	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.52	Pathogenic	0.01	Affected			0.0834	0.2816		2	0	-1.0	34.02
c.1867C>T	L623F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623F 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 REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No predictions are missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the lack of a benign signal, 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	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-11.655	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.22	Ambiguous	0.2	0.92	Ambiguous	1.07	Ambiguous	0.57	Ambiguous	0.440	Likely Benign	-3.98	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.02	Affected			0.0838	0.3016		2	0	-1.0	34.02
c.1873C>T	L625F 2D AIThe SynGAP1 missense variant L625F is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or inconclusive are FoldX, premPS, and Foldetta. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is Uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-12.989	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	1.3	2.26	Destabilizing	1.98	Ambiguous	0.74	Ambiguous	0.479	Likely Benign	-3.82	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.01	Benign	0.01	Affected			0.0586	0.2998		2	0	-1.0	34.02
c.1876A>T	I626F 2D 3DClick to see structure in 3D Viewer AISynGAP1 I626F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Taken together, the overwhelming majority of evidence indicates that I626F is likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-14.483	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	4.37	Destabilizing	0.3	2.12	Destabilizing	3.25	Destabilizing	0.66	Ambiguous	0.631	Likely Pathogenic	-3.78	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.07	Benign	0.00	Affected			0.0481	0.1964		1	0	-1.7	34.02
c.1888A>T	I630F 2D 3DClick to see structure in 3D Viewer AISynGAP1 I630F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that agree on a pathogenic effect comprise SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, and premPS and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting likely pathogenic, and Foldetta yielding an uncertain stability change. Overall, the preponderance of evidence points to a pathogenic impact for I630F. This conclusion is not contradicted by ClinVar, 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	0.040537	Structured	0.036106	Uncertain	0.966	0.236	0.000											-13.669	Likely Pathogenic	0.705	Likely Pathogenic	Likely Benign	2.52	Destabilizing	0.3	0.76	Ambiguous	1.64	Ambiguous	0.75	Ambiguous	0.782	Likely Pathogenic	-3.12	Deleterious	0.935	Possibly Damaging	0.473	Possibly Damaging	-1.46	Pathogenic	0.01	Affected			0.0443	0.1964		1	0	-1.7	34.02
c.1992G>C	L664F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664F resides in the GAP domain. ClinVar lists no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of available predictions support a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-12.834	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.98	Ambiguous	0.3	1.03	Ambiguous	1.51	Ambiguous	0.55	Ambiguous	0.355	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.05	Benign	0.03	Affected			0.0537	0.2311		2	0	-1.0	34.02
c.1992G>T	L664F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664F resides in the GAP domain. ClinVar lists no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of available predictions support a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-12.834	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.98	Ambiguous	0.3	1.03	Ambiguous	1.51	Ambiguous	0.55	Ambiguous	0.355	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.05	Benign	0.03	Affected			0.0537	0.2311		2	0	-1.0	34.02
c.1999A>T	I667F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I667F missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign calls are limited to FATHMM, while the remaining 11 predictors—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a pathogenic effect. No prediction is inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-14.389	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	7.55	Destabilizing	0.3	1.80	Ambiguous	4.68	Destabilizing	0.86	Ambiguous	0.569	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.790	Possibly Damaging	2.96	Benign	0.00	Affected			0.0668	0.2648		1	0	-1.7	34.02
c.2047A>T	I683F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, while AlphaMissense‑Optimized and Foldetta are inconclusive and thus treated as unavailable evidence. Overall, the balance of evidence favors a pathogenic classification for I683F, and this assessment 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	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-12.781	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous	1.38	Ambiguous	0.1	-0.23	Likely Benign	0.58	Ambiguous	0.59	Ambiguous	0.481	Likely Benign	-3.99	Deleterious	0.971	Probably Damaging	0.499	Possibly Damaging	3.27	Benign	0.01	Affected			0.0770	0.2307		1	0	-1.7	34.02
c.2055G>C	L685F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685F is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX and Rosetta predictions are uncertain and are treated as unavailable. Overall, the preponderance of evidence points to a pathogenic impact for the variant, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.304	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.62	Ambiguous	0.2	1.80	Ambiguous	1.71	Ambiguous	0.50	Likely Benign	0.300	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.33	Benign	0.01	Affected			0.0724	0.2367		2	0	-1.0	34.02
c.2055G>T	L685F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685F is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX and Rosetta predictions are uncertain and are treated as unavailable. Overall, the preponderance of evidence points to a pathogenic impact for the variant, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.304	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.62	Ambiguous	0.2	1.80	Ambiguous	1.71	Ambiguous	0.50	Likely Benign	0.300	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.33	Benign	0.01	Affected			0.0724	0.2367		2	0	-1.0	34.02
c.205A>T	I69F 2D AIThe SynGAP1 missense variant I69F is reported in gnomAD (variant ID 6‑33425813‑A‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is also benign. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that I69F is most likely benign, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.466129	Uncertain	0.437	0.786	0.375								6-33425813-A-T	2	1.24e-6	-3.747	Likely Benign	0.251	Likely Benign	Likely Benign										0.104	Likely Benign	-0.99	Neutral	0.824	Possibly Damaging	0.507	Possibly Damaging	4.12	Benign	0.00	Affected	4.32	1	0.0412	0.2743		0	1	-1.7	34.02
c.2065C>T	L689F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Two tools (Rosetta and premPS) yield uncertain results. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-9.817	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	2.45	Destabilizing	0.2	1.95	Ambiguous	2.20	Destabilizing	0.67	Ambiguous	0.286	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.860	Possibly Damaging	3.18	Benign	0.00	Affected			0.0608	0.2891		2	0	-1.0	34.02
c.2086C>T	L696F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L696F has no ClinVar entry and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 benign. 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	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-9.651	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.14	Likely Benign	0.1	0.74	Ambiguous	0.44	Likely Benign	0.55	Ambiguous	0.422	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.05	Benign	0.00	Affected			0.0667	0.2008		2	0	-1.0	34.02
c.2107C>T	L703F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta remains unavailable. Overall, the majority of reliable predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.929	Likely Pathogenic	0.768	Likely Pathogenic	Likely Benign	1.03	Ambiguous	0.1	0.59	Ambiguous	0.81	Ambiguous	0.50	Likely Benign	0.247	Likely Benign	-3.25	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.12	Benign	0.00	Affected			0.0600	0.2555		2	0	-1.0	34.02
c.2122C>T	L708F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L708F is not reported in ClinVar and is present in gnomAD (ID 6‑33441587‑C‑T). Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions are limited to polyPhen‑2 HumDiv and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) return uncertain or no result. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta indicates no significant destabilization (uncertain). Overall, the preponderance of evidence supports a benign effect for L708F, 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.		GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000								6-33441587-C-T	2	1.24e-6	-9.154	Likely Pathogenic	0.436	Ambiguous	Likely Benign	1.48	Ambiguous	0.3	0.93	Ambiguous	1.21	Ambiguous	0.37	Likely Benign	0.110	Likely Benign	-2.46	Neutral	0.931	Possibly Damaging	0.326	Benign	3.29	Benign	0.07	Tolerated	3.50	9	0.0497	0.2366		0	2	-1.0	34.02
c.2149C>T	L717F 2D AIThe SynGAP1 missense variant L717F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. No folding‑stability metrics (FoldX, Rosetta, premPS) provide decisive evidence. 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	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-10.917	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.6	0.59	Ambiguous	0.67	Ambiguous	0.63	Ambiguous	0.157	Likely Benign	-2.56	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.36	Benign	0.02	Affected			0.0444	0.2207		2	0	-1.0	34.02
c.2152C>T	L718F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718F lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas the remaining tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; premPS is uncertain and is not counted as evidence. 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) also predicts pathogenic. Based on the overwhelming consensus of these 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	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.302	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.87	Destabilizing	0.2	2.64	Destabilizing	3.26	Destabilizing	0.78	Ambiguous	0.347	Likely Benign	-3.73	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0590	0.2979		2	0	-1.0	34.02
c.2161A>T	I721F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact, while premPS remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these 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	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-12.559	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	4.61	Destabilizing	0.1	2.74	Destabilizing	3.68	Destabilizing	0.66	Ambiguous	0.295	Likely Benign	-3.74	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.0420	0.2931		1	0	-1.7	34.02
c.2188A>T	I730F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730F has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or tolerated. Only polyPhen2_HumDiv classifies the change as pathogenic. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, reports a benign effect. No prediction tool or stability analysis is inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-4.953	Likely Benign	0.173	Likely Benign	Likely Benign	-0.54	Ambiguous	0.1	-0.01	Likely Benign	-0.28	Likely Benign	-0.01	Likely Benign	0.055	Likely Benign	-1.86	Neutral	0.699	Possibly Damaging	0.152	Benign	3.45	Benign	0.08	Tolerated			0.0509	0.2082		1	0	-1.7	34.02
c.2287C>T	L763F 2D AIThe SynGAP1 missense variant L763F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. There is no ClinVar entry to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-4.127	Likely Benign	0.255	Likely Benign	Likely Benign										0.091	Likely Benign	-0.71	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.39	Pathogenic	0.19	Tolerated			0.0584	0.3140		2	0	-1.0	34.02
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.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.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.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.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.2479A>T	I827F 2D AIThe SynGAP1 missense variant I827F 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, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.636272	Binding	0.383	0.884	0.625											-4.799	Likely Benign	0.517	Ambiguous	Likely Benign										0.155	Likely Benign	-1.30	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.09	Tolerated			0.0490	0.2306		1	0	-1.7	34.02
c.2538A>C	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Overall, the preponderance of evidence from multiple high‑accuracy predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2538A>T	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic or deleterious impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.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.2643G>C	L881F 2D AIThe SynGAP1 missense variant L881F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for L881F, 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		0.703578	Disordered	0.629350	Binding	0.299	0.874	0.250											-5.759	Likely Benign	0.101	Likely Benign	Likely Benign										0.044	Likely Benign	-0.87	Neutral	0.818	Possibly Damaging	0.360	Benign	2.48	Pathogenic	0.02	Affected			0.0711	0.3415		2	0	-1.0	34.02
c.2643G>T	L881F 2D AIThe SynGAP1 missense variant L881F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for L881F, 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		0.703578	Disordered	0.629350	Binding	0.299	0.874	0.250											-5.759	Likely Benign	0.101	Likely Benign	Likely Benign										0.044	Likely Benign	-0.87	Neutral	0.818	Possibly Damaging	0.360	Benign	2.48	Pathogenic	0.02	Affected			0.0711	0.3415		2	0	-1.0	34.02
c.2671C>T	L891F 2D AIThe SynGAP1 missense variant L891F 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. Overall, the majority of evidence points to a benign effect for L891F, 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		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-5.650	Likely Benign	0.126	Likely Benign	Likely Benign										0.102	Likely Benign	-1.80	Neutral	0.970	Probably Damaging	0.744	Possibly Damaging	2.66	Benign	0.04	Affected			0.0652	0.2907		2	0	-1.0	34.02
c.2695A>T	I899F 2D AIThe SynGAP1 missense variant I899F 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		0.675549	Disordered	0.443727	Uncertain	0.292	0.928	0.375											-4.049	Likely Benign	0.161	Likely Benign	Likely Benign										0.060	Likely Benign	-1.05	Neutral	0.906	Possibly Damaging	0.473	Possibly Damaging	2.69	Benign	0.01	Affected			0.0593	0.2435		1	0	-1.7	34.02
c.2716C>T	L906F 2D AIThe SynGAP1 missense variant L906F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-4.700	Likely Benign	0.304	Likely Benign	Likely Benign										0.113	Likely Benign	-1.79	Neutral	0.999	Probably Damaging	0.979	Probably Damaging	2.22	Pathogenic	0.18	Tolerated			0.0753	0.3342		2	0	-1.0	34.02
c.2767A>T	I923F 2D AIThe SynGAP1 missense variant I923F 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		0.562014	Disordered	0.964857	Binding	0.292	0.852	0.250											-2.967	Likely Benign	0.169	Likely Benign	Likely Benign										0.112	Likely Benign	-0.85	Neutral	0.007	Benign	0.005	Benign	2.70	Benign	0.11	Tolerated			0.0726	0.3887		1	0	-1.7	34.02
c.2773C>T	L925F 2D AIThe SynGAP1 missense variant L925F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic impact for the L925F substitution, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-4.147	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0897	0.2881		2	0	-1.0	34.02
c.2791C>T	L931F 2D AIThe SynGAP1 missense variant L931F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a 2‑to‑2 split, leaving the consensus inconclusive. Foldetta, which assesses protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Consequently, the overall evidence leans toward pathogenicity, driven by the majority of standard predictors, and does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-5.101	Likely Benign	0.790	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.04	Affected			0.0718	0.3208		2	0	-1.0	34.02
c.2962C>T	L988F 2D AIThe SynGAP1 missense variant L988F is listed in ClinVar (ID 968833.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443514‑C‑T). 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 and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” classification. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750					Uncertain		1	6-33443514-C-T	1	6.20e-7	-4.368	Likely Benign	0.356	Ambiguous	Likely Benign										0.135	Likely Benign	-1.70	Neutral	0.977	Probably Damaging	0.900	Possibly Damaging	2.69	Benign	0.00	Affected	4.32	2	0.0693	0.3592		2	0	-1.0	34.02
c.2998A>T	I1000F 2D AIThe SynGAP1 missense variant I1000F is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates that I1000F 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		0.745909	Disordered	0.957020	Binding	0.293	0.904	0.625											-3.801	Likely Benign	0.201	Likely Benign	Likely Benign										0.147	Likely Benign	-1.02	Neutral	0.968	Probably Damaging	0.713	Possibly Damaging	2.70	Benign	0.13	Tolerated			0.0594	0.3259		1	0	-1.7	34.02
c.3001C>T	L1001F 2D AIThe SynGAP1 missense variant L1001F 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, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority vote of the four high‑confidence tools) is benign; Foldetta data are unavailable. Overall, the preponderance of evidence supports a benign classification for L1001F, and this conclusion does not conflict with ClinVar, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375											-4.712	Likely Benign	0.119	Likely Benign	Likely Benign										0.026	Likely Benign	-0.85	Neutral	0.934	Possibly Damaging	0.617	Possibly Damaging	2.65	Benign	0.00	Affected			0.0703	0.2876		2	0	-1.0	34.02
c.3064C>T	L1022F 2D AIThe SynGAP1 missense variant L1022F is reported in gnomAD (variant ID 6‑33443616‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500								6-33443616-C-T	2	1.24e-6	-5.035	Likely Benign	0.351	Ambiguous	Likely Benign										0.072	Likely Benign	-1.84	Neutral	0.971	Probably Damaging	0.801	Possibly Damaging	2.51	Benign	0.07	Tolerated	3.77	5	0.0730	0.4231		0	2	-1.0	34.02
c.306G>C	L102F 2D AIThe SynGAP1 missense variant L102F 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		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-4.712	Likely Benign	0.094	Likely Benign	Likely Benign										0.144	Likely Benign	-0.80	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.13	Benign	0.00	Affected			0.0863	0.3205		2	0	-1.0	34.02
c.306G>T	L102F 2D AIThe SynGAP1 missense variant L102F 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		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-4.712	Likely Benign	0.094	Likely Benign	Likely Benign										0.153	Likely Benign	-0.80	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.13	Benign	0.00	Affected			0.0863	0.3205		2	0	-1.0	34.02
c.3070C>T	L1024F 2D AIThe SynGAP1 missense variant L1024F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains both benign and pathogenic calls. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-5.133	Likely Benign	0.544	Ambiguous	Likely Benign										0.059	Likely Benign	-2.08	Neutral	0.994	Probably Damaging	0.924	Probably Damaging	2.40	Pathogenic	0.07	Tolerated			0.0706	0.3708		2	0	-1.0	34.02
c.3109A>T	I1037F 2D AIThe SynGAP1 missense variant I1037F is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in‑silico predictors shows a split: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy tools further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment is consistent with the absence of a ClinVar pathogenic claim. Thus, the variant is most likely benign, and this conclusion does not contradict ClinVar, which has no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.939629	Disordered	0.986140	Binding	0.309	0.774	0.625											-3.517	Likely Benign	0.653	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-0.97	Neutral	0.977	Probably Damaging	0.632	Possibly Damaging	2.71	Benign	0.16	Tolerated			0.0653	0.3722		1	0	-1.7	34.02
c.3115A>T	I1039F 2D AIThe SynGAP1 missense variant I1039F is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign interpretation: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) indicate pathogenic. When predictions are grouped by agreement, the benign‑oriented tools outnumber the pathogenic ones, and the single uncertain call from AlphaMissense‑Default does not alter this balance. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. Foldetta data are unavailable. Overall, the computational evidence overwhelmingly supports a benign 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		0.969315	Disordered	0.979204	Binding	0.292	0.806	0.625											-2.872	Likely Benign	0.545	Ambiguous	Likely Benign										0.124	Likely Benign	-1.16	Neutral	0.925	Possibly Damaging	0.510	Possibly Damaging	2.68	Benign	0.13	Tolerated			0.0710	0.4368		1	0	-1.7	34.02
c.3204G>C	L1068F 2D AIThe SynGAP1 missense variant L1068F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) favor a benign classification. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.947281	Disordered	0.981041	Binding	0.362	0.907	0.875											-6.338	Likely Benign	0.182	Likely Benign	Likely Benign										0.107	Likely Benign	-1.38	Neutral	0.934	Possibly Damaging	0.537	Possibly Damaging	2.49	Pathogenic	0.00	Affected			0.0754	0.4202		2	0	-1.0	34.02
c.3204G>T	L1068F 2D AIThe SynGAP1 missense variant L1068F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) favor a benign classification. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.947281	Disordered	0.981041	Binding	0.362	0.907	0.875											-6.338	Likely Benign	0.182	Likely Benign	Likely Benign										0.106	Likely Benign	-1.38	Neutral	0.934	Possibly Damaging	0.537	Possibly Damaging	2.49	Pathogenic	0.00	Affected			0.0754	0.4202		2	0	-1.0	34.02
c.3228G>C	L1076F 2D AIThe SynGAP1 missense variant L1076F 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, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-4.606	Likely Benign	0.675	Likely Pathogenic	Likely Benign										0.092	Likely Benign	-0.92	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.42	Pathogenic	0.03	Affected			0.0759	0.3767		2	0	-1.0	34.02
c.3228G>T	L1076F 2D AIThe SynGAP1 missense variant L1076F 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, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-4.606	Likely Benign	0.675	Likely Pathogenic	Likely Benign										0.092	Likely Benign	-0.92	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.42	Pathogenic	0.03	Affected			0.0759	0.3767		2	0	-1.0	34.02
c.3276G>C	L1092F 2D AIThe SynGAP1 missense variant L1092F is reported in gnomAD (6‑33443828‑G‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000								6-33443828-G-C	1	6.40e-7	-5.010	Likely Benign	0.623	Likely Pathogenic	Likely Benign										0.067	Likely Benign	-1.40	Neutral	0.986	Probably Damaging	0.823	Possibly Damaging	2.63	Benign	0.18	Tolerated	3.77	5	0.0772	0.4060		0	2	-1.0	34.02
c.3276G>T	L1092F 2D AIThe SynGAP1 missense variant L1092F is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools show a split: benign calls from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also leans benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000											-5.010	Likely Benign	0.623	Likely Pathogenic	Likely Benign										0.067	Likely Benign	-1.40	Neutral	0.986	Probably Damaging	0.823	Possibly Damaging	2.63	Benign	0.18	Tolerated	3.77	5	0.0772	0.4060		0	2	-1.0	34.02
c.3325C>T	L1109F 2D AIThe SynGAP1 missense variant L1109F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875											-3.459	Likely Benign	0.109	Likely Benign	Likely Benign										0.089	Likely Benign	-1.04	Neutral	0.832	Possibly Damaging	0.324	Benign	2.74	Benign	0.12	Tolerated			0.0780	0.4540		2	0	-1.0	34.02
c.3343A>T	I1115F 2D AIThe SynGAP1 missense variant I1115F is reported in gnomAD (ID 6‑33443895‑A‑T) and has no ClinVar entry. All available in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are not available. Based on the unanimous benign predictions and the lack of a ClinVar pathogenic classification, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.892339	Binding	0.308	0.912	0.750								6-33443895-A-T			-3.426	Likely Benign	0.095	Likely Benign	Likely Benign										0.097	Likely Benign	-0.98	Neutral	0.230	Benign	0.098	Benign	2.71	Benign	0.19	Tolerated	4.32	2	0.0769	0.4338		0	1	-1.7	34.02
c.3397A>T	I1133F 2D AIThe SynGAP1 missense variant I1133F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.832785	Binding	0.316	0.892	0.750											-2.941	Likely Benign	0.164	Likely Benign	Likely Benign										0.272	Likely Benign	-1.21	Neutral	0.290	Benign	0.124	Benign	5.45	Benign	0.05	Affected			0.0598	0.3522		1	0	-1.7	34.02
c.3432G>C	L1144F 2D AIThe SynGAP1 missense variant L1144F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the 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		0.950334	Disordered	0.726803	Binding	0.277	0.840	1.000											-4.375	Likely Benign	0.406	Ambiguous	Likely Benign										0.415	Likely Benign	-1.71	Neutral	0.999	Probably Damaging	0.969	Probably Damaging	5.69	Benign	0.04	Affected			0.0685	0.3283		2	0	-1.0	34.02
c.3432G>T	L1144F 2D AIThe SynGAP1 missense variant L1144F is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the aggregate evidence, the variant is most likely benign. This assessment does not contradict 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		0.950334	Disordered	0.726803	Binding	0.277	0.840	1.000											-4.375	Likely Benign	0.406	Ambiguous	Likely Benign										0.415	Likely Benign	-1.71	Neutral	0.999	Probably Damaging	0.969	Probably Damaging	5.69	Benign	0.04	Affected			0.0685	0.3283		2	0	-1.0	34.02
c.3502A>T	I1168F 2D AIThe SynGAP1 missense variant I1168F is not reported in ClinVar and is absent from gnomAD. Prediction tools show a mixed signal: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments are limited: AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Considering the majority of individual predictors and the SGM‑Consensus outcome, the variant is most likely benign. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500											-3.422	Likely Benign	0.879	Likely Pathogenic	Ambiguous										0.440	Likely Benign	-1.21	Neutral	0.998	Probably Damaging	0.958	Probably Damaging	5.45	Benign	0.04	Affected			0.0616	0.3524		1	0	-1.7	34.02
c.3517A>T	I1173F 2D AIThe SynGAP1 missense variant I1173F 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 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for I1173F, 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	Coiled-coil	0.501700	Disordered	0.653145	Binding	0.521	0.756	0.375											-3.635	Likely Benign	0.491	Ambiguous	Likely Benign										0.365	Likely Benign	-0.87	Neutral	0.934	Possibly Damaging	0.636	Possibly Damaging	5.39	Benign	0.13	Tolerated			0.0567	0.2108		1	0	-1.7	34.02
c.3538C>T	L1180F 2D AIThe SynGAP1 missense variant L1180F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of high‑accuracy predictions lean toward a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-5.370	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.077	Likely Benign	-1.29	Neutral	0.749	Possibly Damaging	0.444	Benign	2.65	Benign	0.00	Affected			0.0516	0.2345		2	0	-1.0	34.02
c.3604A>T	I1202F 2D AIThe SynGAP1 missense variant I1202F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-12.304	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.23	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.02	Affected			0.0583	0.2079		1	0	-1.7	34.02
c.3697A>T	I1233F 2D AIThe SynGAP1 missense variant I1233F is not 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 assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, more tools predict pathogenicity (five) than benignity (three), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.525368	Disordered	0.564054	Binding	0.881	0.531	0.125											-8.414	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous										0.075	Likely Benign	-2.34	Neutral	0.968	Probably Damaging	0.713	Possibly Damaging	2.56	Benign	0.03	Affected			0.0418	0.2731		1	0	-1.7	34.02
c.3775A>T	I1259F 2D AIThe SynGAP1 missense variant I1259F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized returns an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.666	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-1.68	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.55	Benign	0.03	Affected			0.0428	0.2563		1	0	-1.7	34.02
c.3784A>T	I1262F 2D AIThe SynGAP1 missense variant I1262F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, 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 outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-11.343	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.515	Likely Pathogenic	-3.32	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0532	0.2731		1	0	-1.7	34.02
c.3787A>T	I1263F 2D AIThe SynGAP1 missense variant I1263F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Because the majority of evidence points to a deleterious effect and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-5.887	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.335	Likely Benign	-3.32	Deleterious	0.968	Probably Damaging	0.637	Possibly Damaging	1.81	Pathogenic	0.00	Affected			0.0494	0.2375		1	0	-1.7	34.02
c.37A>T	I13F 2D AIThe SynGAP1 missense variant I13F is not reported 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		0.486429	Structured	0.482657	Uncertain	0.318	0.916	0.375											-3.359	Likely Benign	0.126	Likely Benign	Likely Benign										0.134	Likely Benign	-0.09	Neutral	0.107	Benign	0.010	Benign	4.04	Benign	0.00	Affected			0.0654	0.3972		1	0	-1.7	34.02
c.3874C>T	L1292F 2D AIThe SynGAP1 missense variant L1292F is reported in gnomAD (ID 6‑33447922‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates 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 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		0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625								6-33447922-C-T			-5.759	Likely Benign	0.200	Likely Benign	Likely Benign										0.097	Likely Benign	-1.88	Neutral	0.611	Possibly Damaging	0.329	Benign	2.49	Pathogenic	0.03	Affected	3.77	5	0.0707	0.2799		0	2	-1.0	34.02
c.3895C>T	L1299F 2D AIThe SynGAP1 missense variant L1299F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-5.618	Likely Benign	0.171	Likely Benign	Likely Benign										0.138	Likely Benign	-1.80	Neutral	0.002	Benign	0.005	Benign	2.69	Benign	0.42	Tolerated			0.0707	0.3342		2	0	-1.0	34.02
c.3906G>C	L1302F 2D AISynGAP1 missense variant L1302F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments indicate AlphaMissense‑Optimized predicts benign, whereas the SGM consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta stability analysis is unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic effect. Thus, the variant is most likely pathogenic, a conclusion that contrasts with its current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.889642	Binding	0.429	0.842	0.875					Uncertain		1				-5.674	Likely Benign	0.148	Likely Benign	Likely Benign										0.211	Likely Benign	-2.70	Deleterious	0.960	Probably Damaging	0.657	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.0721	0.2648		2	0	-1.0	34.02
c.3906G>T	L1302F 2D AIThe SynGAP1 missense variant L1302F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools that are available indicate a benign outcome (AlphaMissense‑Optimized) while the consensus and stability analyses are missing. Consequently, the overall prediction is ambiguous, but the most reliable evidence points toward a benign effect, and this does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.889642	Binding	0.429	0.842	0.875											-5.674	Likely Benign	0.148	Likely Benign	Likely Benign										0.215	Likely Benign	-2.70	Deleterious	0.960	Probably Damaging	0.657	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.0721	0.2648		2	0	-1.0	34.02
c.3991A>T	I1331F 2D AIThe SynGAP1 missense variant I1331F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.220	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.46	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	3.31	Benign	0.00	Affected			0.0522	0.3225		1	0	-1.7	34.02
c.421A>T	I141F 2D AIThe SynGAP1 missense variant I141F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-9.621	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.221	Likely Benign	-1.82	Neutral	0.001	Benign	0.002	Benign	3.57	Benign	0.01	Affected			0.0489	0.2775		1	0	-1.7	34.02
c.448C>T	L150F 2D AIThe SynGAP1 missense variant L150F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM‑Consensus suggests that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-12.459	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-2.56	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.69	Benign	0.00	Affected			0.0580	0.3112		2	0	-1.0	34.02
c.475A>T	I159F 2D AIThe SynGAP1 missense variant I159F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence, particularly from the high‑accuracy tools, points to a benign impact. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-9.530	Likely Pathogenic	0.447	Ambiguous	Likely Benign										0.200	Likely Benign	-1.41	Neutral	0.995	Probably Damaging	0.979	Probably Damaging	3.87	Benign	0.00	Affected			0.0490	0.2446		1	0	-1.7	34.02
c.558G>C	L186F 2D AIThe SynGAP1 missense variant L186F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500					Uncertain		1				-11.861	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.132	Likely Benign	-3.03	Deleterious	0.009	Benign	0.012	Benign	3.50	Benign	0.00	Affected			0.0524	0.3177		2	0	-1.0	34.02
c.558G>T	L186F 2D AIThe SynGAP1 missense variant L186F has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “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 indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-11.861	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.132	Likely Benign	-3.03	Deleterious	0.009	Benign	0.012	Benign	3.50	Benign	0.00	Affected			0.0524	0.3177		2	0	-1.0	34.02
c.588G>C	L196F 2D AIThe SynGAP1 missense variant L196F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-10.245	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.177	Likely Benign	-3.17	Deleterious	0.917	Possibly Damaging	0.502	Possibly Damaging	3.64	Benign	0.01	Affected			0.0557	0.2756		2	0	-1.0	34.02
c.588G>T	L196F 2D AIThe SynGAP1 missense variant L196F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-10.245	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.177	Likely Benign	-3.17	Deleterious	0.917	Possibly Damaging	0.502	Possibly Damaging	3.64	Benign	0.01	Affected			0.0557	0.2756		2	0	-1.0	34.02
c.592C>T	L198F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198F has no ClinVar entry and is absent from gnomAD. Functional prediction tools split into two consensus groups: benign predictions come from REVEL, Rosetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments are mixed: AlphaMissense‑Optimized and Foldetta report uncertain results, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. No evidence from ClinVar contradicts these findings. Overall, the preponderance of pathogenic predictions and the SGM‑Consensus designation suggest that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-10.602	Likely Pathogenic	0.930	Likely Pathogenic	Ambiguous	1.03	Ambiguous	0.2	0.27	Likely Benign	0.65	Ambiguous	0.00	Likely Benign	0.282	Likely Benign	-3.33	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.39	Benign	0.00	Affected			0.0586	0.3112		2	0	-1.0	34.02
c.600G>C	L200F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L200F is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33435242‑G‑C). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125					Uncertain		1	6-33435242-G-C	2	1.24e-6	-7.606	In-Between	0.592	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.5	1.45	Ambiguous	1.23	Ambiguous	0.43	Likely Benign	0.094	Likely Benign	-1.97	Neutral	0.997	Probably Damaging	0.916	Probably Damaging	4.02	Benign	0.17	Tolerated	3.46	9	0.0640	0.3120		2	0	-1.0	34.02	250.4	-15.1	0.6	0.2	0.5	0.0						X		Uncertain	Leu200, a hydrophobic residue located in the N-terminal loop before the first anti-parallel β sheet strand (res. Ile205-Pro208), is replaced by another hydrophobic residue, phenylalanine. Both the phenyl group of Phe200 and the branched iso-butyl hydrocarbon sidechain of Leu200 occupy an inward hydrophobic niche (e.g., Leu246, Val222, Phe231) during the simulations. However, since the model ends abruptly at the N-terminus, no definite conclusions can be drawn from the simulations.
c.600G>T	L200F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L200F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, ESM1b, Foldetta) returned uncertain results and are not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (benign)—is benign; Foldetta remains uncertain and is treated as unavailable. Overall, the balance of evidence (six benign vs. three pathogenic predictions, with a benign consensus from high‑accuracy methods) indicates that 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.		PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-7.606	In-Between	0.592	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.5	1.45	Ambiguous	1.23	Ambiguous	0.43	Likely Benign	0.094	Likely Benign	-1.97	Neutral	0.997	Probably Damaging	0.916	Probably Damaging	4.02	Benign	0.17	Tolerated	3.46	9	0.0640	0.3120		2	0	-1.0	34.02	250.4	-15.1	0.6	0.2	0.5	0.0						X		Uncertain	Leu200, a hydrophobic residue located in the N-terminal loop before the first anti-parallel β sheet strand (res. Ile205-Pro208), is replaced by another hydrophobic residue, phenylalanine. Both the phenyl group of Phe200 and the branched iso-butyl hydrocarbon sidechain of Leu200 occupy an inward hydrophobic niche (e.g., Leu246, Val222, Phe231) during the simulations. However, since the model ends abruptly at the N-terminus, no definite conclusions can be drawn from the simulations.
c.613A>T	I205F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I205F missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, and polyPhen‑2 HumVar all classify it as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. Uncertain results from Foldetta, premPS, ESM1b, and Rosetta are treated as unavailable. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, while Foldetta remains uncertain. Overall, the consensus of the majority of tools indicates that the variant is most likely benign, 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	PH	0.264545	Structured	0.409933	Uncertain	0.821	0.414	0.125											-7.913	In-Between	0.271	Likely Benign	Likely Benign	0.30	Likely Benign	0.3	0.89	Ambiguous	0.60	Ambiguous	0.52	Ambiguous	0.113	Likely Benign	-1.80	Neutral	0.838	Possibly Damaging	0.368	Benign	4.08	Benign	0.10	Tolerated			0.0461	0.2205		1	0	-1.7	34.02
c.616A>T	I206F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I206F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect comprise SGM‑Consensus, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta. Predictions that are uncertain or inconclusive are FoldX and premPS. High‑accuracy methods all support a deleterious outcome: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-12.669	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	1.82	Ambiguous	0.4	3.39	Destabilizing	2.61	Destabilizing	0.70	Ambiguous	0.133	Likely Benign	-3.40	Deleterious	0.838	Possibly Damaging	0.368	Benign	3.64	Benign	0.01	Affected			0.0428	0.2721		1	0	-1.7	34.02
c.637A>T	I213F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I213F missense variant is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, while the remaining evaluated algorithms (SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; FoldX and premPS are uncertain and are treated as unavailable evidence. 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 uncertain and thus not considered. Overall, the preponderance of evidence indicates that 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	PH	0.158265	Structured	0.372201	Uncertain	0.850	0.295	0.125											-12.212	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.7	2.66	Destabilizing	1.81	Ambiguous	0.73	Ambiguous	0.815	Likely Pathogenic	-3.30	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.79	Benign	0.01	Affected			0.0473	0.2560		1	0	-1.7	34.02
c.727A>T	I243F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I243F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give inconclusive results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus unavailable; Foldetta is uncertain. Overall, the majority of available predictions (7 pathogenic vs. 3 benign) indicate a likely pathogenic impact. This assessment does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.363090	Structured	0.344471	Uncertain	0.842	0.347	0.000											-12.559	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	2.92	Destabilizing	2.5	0.53	Ambiguous	1.73	Ambiguous	0.42	Likely Benign	0.793	Likely Pathogenic	-2.21	Neutral	0.985	Probably Damaging	0.724	Possibly Damaging	5.53	Benign	0.02	Affected			0.0409	0.2205		1	0	-1.7	34.02
c.802A>T	I268F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; only Rosetta and Foldetta are uncertain. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) remains uncertain. Overall, the consensus of available predictions strongly supports a pathogenic classification for I268F, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-11.426	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.7	0.59	Ambiguous	1.72	Ambiguous	1.00	Destabilizing	0.685	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0427	0.2158		1	0	-1.7	34.02
c.850C>T	L284F 2D AIThe SynGAP1 missense variant L284F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Taken together, the overwhelming majority of evidence indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-11.656	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	1.9	1.05	Ambiguous	1.55	Ambiguous	0.62	Ambiguous	0.654	Likely Pathogenic	-3.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.01	Affected			0.0515	0.2779		2	0	-1.0	34.02
c.1091C>A	P364H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P364H is reported in gnomAD (ID 6‑33437996‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. The protein‑folding stability predictor Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437996-C-A			-10.744	Likely Pathogenic	0.632	Likely Pathogenic	Likely Benign	1.65	Ambiguous	0.9	0.25	Likely Benign	0.95	Ambiguous	0.77	Ambiguous	0.407	Likely Benign	-6.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.02	Affected	3.39	20	0.1800	0.4584		-2	0	-1.6	40.02
c.1238C>A	P413H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413H 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, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact; Rosetta is uncertain. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among pathogenic predictors and the high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-13.376	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.89	Destabilizing	1.0	1.85	Ambiguous	3.37	Destabilizing	1.07	Destabilizing	0.546	Likely Pathogenic	-8.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.16	Benign	0.00	Affected			0.1745	0.3480		0	-2	-1.6	40.02
c.125C>A	P42H 2D AIThe SynGAP1 missense variant P42H 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	0.431487	Uncertain	0.420	0.771	0.375											-3.088	Likely Benign	0.167	Likely Benign	Likely Benign										0.140	Likely Benign	-1.95	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	4.16	Benign	0.00	Affected			0.1995	0.3705		0	-2	-1.6	40.02
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.137C>A	P46H 2D AIThe SynGAP1 missense variant P46H is evaluated by multiple in silico tools. Consensus from SGM‑Consensus indicates a likely benign effect, and the variant is not reported in ClinVar or gnomAD. Functional predictors that agree on a benign outcome include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Predictors that flag a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports likely benign, while Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for P46H, and this conclusion is not contradicted by any ClinVar annotation. The variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.390993	Structured	0.433588	Uncertain	0.549	0.741	0.375											-4.022	Likely Benign	0.428	Ambiguous	Likely Benign										0.097	Likely Benign	-0.43	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	4.10	Benign	0.00	Affected			0.2360	0.5229		0	-2	-1.6	40.02
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.1814C>A	P605H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605H is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a benign outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available predictions are consistent and indicate a deleterious effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000											-13.846	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	8.80	Destabilizing	2.7	6.69	Destabilizing	7.75	Destabilizing	0.87	Ambiguous	0.828	Likely Pathogenic	-8.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.1778	0.4142		0	-2	-1.6	40.02
c.197C>A	P66H 2D AIThe SynGAP1 missense variant P66H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus result is benign; Foldetta predictions are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-4.134	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-2.26	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	3.89	Benign	0.00	Affected			0.1914	0.4675		0	-2	-1.6	40.02
c.2102C>A	P701H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701H missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict the ClinVar status, which contains no pathogenic assertion for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-8.786	Likely Pathogenic	0.553	Ambiguous	Likely Benign	1.40	Ambiguous	0.0	-0.41	Likely Benign	0.50	Ambiguous	0.62	Ambiguous	0.141	Likely Benign	-2.12	Neutral	0.936	Possibly Damaging	0.539	Possibly Damaging	3.38	Benign	0.03	Affected			0.1495	0.3495		0	-2	-1.6	40.02
c.2144C>A	P715H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of predictors (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) indicate a pathogenic impact. Tools with inconclusive results (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 consensus of the majority of evidence points to a pathogenic effect for P715H. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-10.523	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	2.80	Destabilizing	0.0	0.28	Likely Benign	1.54	Ambiguous	0.56	Ambiguous	0.271	Likely Benign	-7.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.37	Benign	0.00	Affected			0.1413	0.3684		0	-2	-1.6	40.02
c.2183C>A	P728H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which predict a deleterious impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic effect for P728H, and this conclusion does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-8.897	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.94	Ambiguous	0.0	0.86	Ambiguous	0.90	Ambiguous	0.64	Ambiguous	0.402	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1993	0.3016		0	-2	-1.6	40.02
c.2222C>A	P741H 2D AIThe SynGAP1 missense variant P741H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875											-5.592	Likely Benign	0.085	Likely Benign	Likely Benign										0.099	Likely Benign	-0.99	Neutral	0.006	Benign	0.007	Benign	2.81	Benign	0.01	Affected			0.1372	0.3831		0	-2	-1.6	40.02
c.2228C>A	P743H 2D AIThe SynGAP1 missense variant P743H 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 computational evidence points to a benign effect for P743H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.526809	Binding	0.317	0.862	0.875											-5.649	Likely Benign	0.099	Likely Benign	Likely Benign										0.121	Likely Benign	-1.99	Neutral	0.989	Probably Damaging	0.870	Possibly Damaging	2.70	Benign	0.01	Affected			0.1653	0.3762		0	-2	-1.6	40.02
c.2234C>A	P745H 2D AIThe SynGAP1 missense variant P745H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875											-5.569	Likely Benign	0.120	Likely Benign	Likely Benign										0.200	Likely Benign	-2.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.53	Benign	0.00	Affected			0.1912	0.3403		0	-2	-1.6	40.02
c.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.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.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.2435C>A	P812H 2D AIThe SynGAP1 missense variant P812H is listed in ClinVar with an uncertain significance and is present in the gnomAD database (ID 6‑33442987‑C‑A). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic outcome; ESM1b remains uncertain. High‑accuracy methods give a benign result from AlphaMissense‑Optimized, a pathogenic consensus from the SGM approach (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta data are unavailable. Overall, the balance of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125					Uncertain		2	6-33442987-C-A	3	1.86e-6	-7.470	In-Between	0.698	Likely Pathogenic	Likely Benign										0.272	Likely Benign	-2.81	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.00	Affected	4.32	4	0.1568	0.4923		0	-2	-1.6	40.02
c.2552C>A	P851H 2D AIThe SynGAP1 missense variant P851H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625											-4.730	Likely Benign	0.102	Likely Benign	Likely Benign										0.184	Likely Benign	0.19	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	4.18	Benign	0.15	Tolerated			0.1577	0.5378		0	-2	-1.6	40.02
c.2654C>A	P885H 2D AIThe SynGAP1 missense variant P885H 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 (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, including the high‑accuracy tools, 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		0.690604	Disordered	0.636133	Binding	0.344	0.917	0.250											-5.239	Likely Benign	0.171	Likely Benign	Likely Benign										0.083	Likely Benign	-1.68	Neutral	0.938	Possibly Damaging	0.749	Possibly Damaging	2.74	Benign	0.00	Affected			0.1552	0.5280		0	-2	-1.6	40.02
c.2660C>A	P887H 2D AIThe SynGAP1 missense variant P887H is not reported 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 P887H, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500											-4.900	Likely Benign	0.136	Likely Benign	Likely Benign										0.072	Likely Benign	-1.71	Neutral	0.977	Probably Damaging	0.777	Possibly Damaging	2.73	Benign	0.13	Tolerated			0.1236	0.3275		0	-2	-1.6	40.02
c.2750C>A	P917H 2D AIThe SynGAP1 missense variant P917H 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 (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—including the high‑accuracy tools—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		0.599170	Disordered	0.863949	Binding	0.314	0.862	0.375											-5.395	Likely Benign	0.182	Likely Benign	Likely Benign										0.122	Likely Benign	-2.00	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.65	Benign	0.00	Affected			0.1584	0.4410		0	-2	-1.6	40.02
c.2771C>A	P924H 2D AIThe SynGAP1 missense variant P924H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of computational evidence indicates that P924H is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.236	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.87	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1317	0.3281		0	-2	-1.6	40.02
c.2789C>A	P930H 2D AIThe SynGAP1 missense variant P930H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors and high‑accuracy tools indicates that P930H is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.824	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.497	Likely Benign	-6.44	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1942	0.4392		0	-2	-1.6	40.02
c.281C>A	P94H 2D AIThe SynGAP1 missense variant P94H is reported in gnomAD (variant ID 6‑33425889‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P94H is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.570978	Binding	0.350	0.869	0.625								6-33425889-C-A	1	6.20e-7	-3.708	Likely Benign	0.106	Likely Benign	Likely Benign										0.077	Likely Benign	-2.31	Neutral	0.637	Possibly Damaging	0.102	Benign	4.11	Benign	0.00	Affected	4.32	1	0.1486	0.3913		-2	0	-1.6	40.02
c.2822C>A	P941H 2D AIThe SynGAP1 missense variant P941H 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, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, two tools—polyPhen‑2 HumDiv and SIFT—classify the change as pathogenic. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.900790	Binding	0.403	0.906	0.625											-4.439	Likely Benign	0.098	Likely Benign	Likely Benign										0.058	Likely Benign	-0.09	Neutral	0.589	Possibly Damaging	0.309	Benign	2.71	Benign	0.00	Affected			0.1621	0.4826		0	-2	-1.6	40.02
c.2861C>A	P954H 2D AIThe SynGAP1 missense variant P954H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar or gnomAD entries—there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984159	Disordered	0.932268	Binding	0.465	0.926	0.750											-3.670	Likely Benign	0.082	Likely Benign	Likely Benign										0.098	Likely Benign	-0.50	Neutral	0.041	Benign	0.067	Benign	2.75	Benign	0.04	Affected			0.2054	0.4756		0	-2	-1.6	40.02
c.2912C>A	P971H 2D AIThe SynGAP1 missense variant P971H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443464‑C‑A). 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; a Foldetta stability prediction is not available. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625					Uncertain		1	6-33443464-C-A	1	6.20e-7	-5.243	Likely Benign	0.086	Likely Benign	Likely Benign										0.039	Likely Benign	-1.11	Neutral	0.898	Possibly Damaging	0.477	Possibly Damaging	3.89	Benign	0.00	Affected	4.32	2	0.1584	0.4858		-2	0	-1.6	40.02
c.2915C>A	P972H 2D AIThe SynGAP1 missense variant P972H 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 also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods 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		0.891961	Disordered	0.954150	Binding	0.472	0.904	0.625											-4.791	Likely Benign	0.087	Likely Benign	Likely Benign										0.049	Likely Benign	-1.62	Neutral	0.589	Possibly Damaging	0.229	Benign	4.19	Benign	0.02	Affected			0.1930	0.4798		0	-2	-1.6	40.02
c.2978C>A	P993H 2D AIThe SynGAP1 missense variant P993H is not reported 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 P993H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.923979	Binding	0.319	0.908	0.750											-4.535	Likely Benign	0.119	Likely Benign	Likely Benign										0.053	Likely Benign	-0.93	Neutral	0.938	Possibly Damaging	0.819	Possibly Damaging	4.11	Benign	0.00	Affected			0.1799	0.4591		0	-2	-1.6	40.02
c.2984C>A	P995H 2D AIThe SynGAP1 missense variant P995H is not reported 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 P995H, 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		0.862302	Disordered	0.935305	Binding	0.338	0.902	0.750											-5.347	Likely Benign	0.107	Likely Benign	Likely Benign										0.044	Likely Benign	-0.75	Neutral	0.832	Possibly Damaging	0.600	Possibly Damaging	4.16	Benign	0.00	Affected			0.1618	0.4571		0	-2	-1.6	40.02
c.2987C>A	P996H 2D AIThe SynGAP1 missense variant P996H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.775545	Disordered	0.942262	Binding	0.312	0.900	0.750											-5.554	Likely Benign	0.103	Likely Benign	Likely Benign										0.045	Likely Benign	-1.19	Neutral	0.001	Benign	0.003	Benign	4.25	Benign	0.00	Affected			0.1585	0.5160		0	-2	-1.6	40.02
c.3035C>A	P1012H 2D AIThe SynGAP1 missense variant P1012H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (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 Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P1012H, 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		0.834292	Disordered	0.894674	Binding	0.319	0.866	0.625											-4.877	Likely Benign	0.087	Likely Benign	Likely Benign										0.024	Likely Benign	-0.38	Neutral	0.832	Possibly Damaging	0.600	Possibly Damaging	2.75	Benign	0.08	Tolerated			0.1553	0.4635		0	-2	-1.6	40.02
c.3101C>A	P1034H 2D AIThe SynGAP1 missense variant P1034H 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. 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 predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.926919	Disordered	0.991713	Binding	0.343	0.752	0.625											-4.634	Likely Benign	0.540	Ambiguous	Likely Benign										0.083	Likely Benign	-3.17	Deleterious	0.938	Possibly Damaging	0.750	Possibly Damaging	2.38	Pathogenic	0.02	Affected			0.1776	0.5451		0	-2	-1.6	40.02
c.3104C>A	P1035H 2D AIThe SynGAP1 missense variant P1035H is not reported in ClinVar and has no entries in gnomAD. Consensus predictions from multiple in‑silico tools are mixed: benign calls come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. No Foldetta stability analysis is available 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		0.945666	Disordered	0.989572	Binding	0.300	0.756	0.625											-5.333	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.058	Likely Benign	-0.76	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	2.68	Benign	0.15	Tolerated			0.1893	0.5669		0	-2	-1.6	40.02
c.3122C>A	P1041H 2D AIThe SynGAP1 missense variant P1041H is not 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), and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, and Foldetta’s protein‑folding stability result is unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status because the variant has not been reported there. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.962114	Disordered	0.967463	Binding	0.345	0.833	0.625											-5.312	Likely Benign	0.377	Ambiguous	Likely Benign										0.476	Likely Benign	-3.32	Deleterious	0.999	Probably Damaging	0.917	Probably Damaging	5.45	Benign	0.03	Affected			0.1883	0.5434		0	-2	-1.6	40.02
c.3137C>A	P1046H 2D AIThe SynGAP1 missense variant P1046H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for P1046H. 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		0.970265	Disordered	0.942366	Binding	0.364	0.898	0.750											-5.715	Likely Benign	0.148	Likely Benign	Likely Benign										0.035	Likely Benign	-1.64	Neutral	0.832	Possibly Damaging	0.670	Possibly Damaging	2.33	Pathogenic	0.07	Tolerated			0.1585	0.5250		0	-2	-1.6	40.02
c.3146C>A	P1049H 2D AIThe SynGAP1 missense variant P1049H 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		0.978316	Disordered	0.917915	Binding	0.428	0.920	0.750											-5.427	Likely Benign	0.115	Likely Benign	Likely Benign										0.066	Likely Benign	-2.06	Neutral	0.978	Probably Damaging	0.750	Possibly Damaging	2.76	Benign	0.01	Affected			0.1800	0.5070		0	-2	-1.6	40.02
c.3197C>A	P1066H 2D AIThe SynGAP1 missense variant P1066H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this 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		0.967676	Disordered	0.968838	Binding	0.403	0.913	0.875											-6.034	Likely Benign	0.185	Likely Benign	Likely Benign										0.146	Likely Benign	-2.90	Deleterious	1.000	Probably Damaging	0.975	Probably Damaging	2.61	Benign	0.00	Affected			0.1984	0.5861		0	-2	-1.6	40.02
c.3251C>A	P1084H 2D AIThe SynGAP1 missense variant P1084H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443803‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which reports “Likely Benign”). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar designation of uncertainty rather than a definitive pathogenic claim. Thus, the variant is most likely benign, and its prediction profile does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.979020	Binding	0.348	0.889	1.000					Uncertain		1	6-33443803-C-A	1	6.31e-7	-4.125	Likely Benign	0.323	Likely Benign	Likely Benign										0.134	Likely Benign	-3.16	Deleterious	0.997	Probably Damaging	0.840	Possibly Damaging	3.96	Benign	0.00	Affected	3.77	5	0.1751	0.5523		-2	0	-1.6	40.02
c.3302C>A	P1101H 2D AIThe SynGAP1 missense variant P1101H 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). 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 result is available. Overall, the majority of evidence points to a benign effect for P1101H, 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		0.874069	Disordered	0.968967	Binding	0.457	0.861	0.875											-5.370	Likely Benign	0.149	Likely Benign	Likely Benign										0.167	Likely Benign	-1.87	Neutral	0.996	Probably Damaging	0.864	Possibly Damaging	4.18	Benign	0.02	Affected			0.2046	0.4597		0	-2	-1.6	40.02
c.3392C>A	P1131H 2D AIThe SynGAP1 missense variant P1131H is not 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, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750											-5.207	Likely Benign	0.454	Ambiguous	Likely Benign										0.357	Likely Benign	-3.50	Deleterious	0.971	Probably Damaging	0.750	Possibly Damaging	5.24	Benign	0.00	Affected			0.1519	0.5546		0	-2	-1.6	40.02
c.3437C>A	P1146H 2D AIThe SynGAP1 missense variant P1146H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign outcome (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method, 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 has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.732173	Binding	0.415	0.837	1.000											-4.428	Likely Benign	0.518	Ambiguous	Likely Benign										0.529	Likely Pathogenic	-4.93	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	5.46	Benign	0.00	Affected			0.1625	0.4512		0	-2	-1.6	40.02
c.3485C>A	P1162H 2D AIThe SynGAP1 missense variant P1162H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as Pathogenic, whereas the SGM‑Consensus (majority vote) indicates Likely Benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction conflicts with the consensus. Because ClinVar contains no entry, there is no contradiction with clinical database status. Based on the collective predictions, the variant is most likely benign, though the AlphaMissense‑Optimized result suggests caution. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-3.733	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.168	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.67	Benign	0.17	Tolerated			0.1481	0.5001		0	-2	-1.6	40.02
c.365C>A	P122H 2D AIThe SynGAP1 missense variant P122H is not reported 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 P122H. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.672358	Binding	0.400	0.887	0.750											-4.993	Likely Benign	0.321	Likely Benign	Likely Benign										0.096	Likely Benign	-1.82	Neutral	0.996	Probably Damaging	0.750	Possibly Damaging	4.14	Benign	0.03	Affected			0.2306	0.4213		0	-2	-1.6	40.02
c.374C>A	P125H 2D AIThe SynGAP1 missense variant P125H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the majority of conventional predictors (five pathogenic vs four benign) lean toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the inconclusive SGM Consensus temper this view. No ClinVar annotation is present, so there is no reported status to contradict the computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.704227	Binding	0.373	0.878	0.625											-5.177	Likely Benign	0.583	Likely Pathogenic	Likely Benign										0.235	Likely Benign	-4.18	Deleterious	0.996	Probably Damaging	0.750	Possibly Damaging	2.82	Benign	0.01	Affected			0.1598	0.4263		0	-2	-1.6	40.02
c.3833C>A	P1278H 2D AIThe SynGAP1 missense variant P1278H is reported in gnomAD (variant ID 6‑33447881‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the same set of benign predictions) is benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.806955	Binding	0.532	0.722	0.750								6-33447881-C-A	7	4.51e-6	-5.691	Likely Benign	0.142	Likely Benign	Likely Benign										0.087	Likely Benign	-1.69	Neutral	0.938	Possibly Damaging	0.477	Possibly Damaging	2.67	Benign	0.01	Affected	3.77	5	0.1997	0.3155		-2	0	-1.6	40.02
c.383C>A	P128H 2D AIThe SynGAP1 missense variant P128H is not reported 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. AlphaMissense‑Default remains uncertain, and 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 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		0.497853	Structured	0.713069	Binding	0.376	0.878	0.625											-4.806	Likely Benign	0.564	Ambiguous	Likely Benign										0.169	Likely Benign	-1.90	Neutral	0.996	Probably Damaging	0.750	Possibly Damaging	4.14	Benign	0.03	Affected			0.2207	0.3414		0	-2	-1.6	40.02
c.3860C>A	P1287H 2D AIThe SynGAP1 missense variant P1287H is recorded in gnomAD (6‑33447908‑C‑A) and has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750								6-33447908-C-A			-3.606	Likely Benign	0.135	Likely Benign	Likely Benign										0.043	Likely Benign	-1.36	Neutral	0.938	Possibly Damaging	0.596	Possibly Damaging	2.80	Benign	0.00	Affected	3.77	5	0.1306	0.3448		-2	0	-1.6	40.02
c.3899C>A	P1300H 2D AIThe SynGAP1 missense variant P1300H 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		0.788093	Disordered	0.885826	Binding	0.400	0.834	0.875											-5.062	Likely Benign	0.140	Likely Benign	Likely Benign										0.093	Likely Benign	-1.48	Neutral	0.990	Probably Damaging	0.840	Possibly Damaging	2.80	Benign	0.01	Affected			0.1757	0.3802		0	-2	-1.6	40.02
c.3902C>A	P1301H 2D AIThe SynGAP1 missense variant P1301H is listed in ClinVar (ID 212356.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451776‑C‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods report a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No Foldetta stability result is available. Overall, the majority of predictions, including the high‑accuracy consensus, support a benign classification, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875					Conflicting		2	6-33451776-C-A	5	3.10e-6	-5.756	Likely Benign	0.104	Likely Benign	Likely Benign										0.232	Likely Benign	-1.13	Neutral	0.642	Possibly Damaging	0.378	Benign	2.79	Benign	0.04	Affected	3.77	5	0.1305	0.2965		0	-2	-1.6	40.02
c.3959C>A	P1320H 2D AIThe SynGAP1 missense variant P1320H is listed in gnomAD (ID 6‑33451833‑C‑A) and has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750								6-33451833-C-A	2	1.29e-6	-6.296	Likely Benign	0.136	Likely Benign	Likely Benign										0.114	Likely Benign	-1.05	Neutral	0.998	Probably Damaging	0.990	Probably Damaging	4.17	Benign	0.00	Affected	3.77	5	0.1955	0.5461		-2	0	-1.6	40.02
c.3974C>A	P1325H 2D AIThe SynGAP1 missense variant P1325H is reported in gnomAD (variant ID 6‑33451848‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No result is available from the Foldetta stability analysis. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.893621	Binding	0.439	0.791	0.875								6-33451848-C-A			-6.970	Likely Benign	0.136	Likely Benign	Likely Benign										0.056	Likely Benign	0.10	Neutral	0.704	Possibly Damaging	0.187	Benign	4.04	Benign	0.00	Affected	4.32	1	0.2103	0.4364		-2	0	-1.6	40.02
c.3980C>A	P1327H 2D AIThe SynGAP1 missense variant P1327H is reported in gnomAD (ID 6‑33451854‑C‑A) and has no ClinVar entry. 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, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Based on the preponderance of evidence from both general and high‑accuracy predictors, 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		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875								6-33451854-C-A			-5.496	Likely Benign	0.263	Likely Benign	Likely Benign										0.144	Likely Benign	-0.49	Neutral	0.998	Probably Damaging	0.953	Probably Damaging	4.09	Benign	0.04	Affected	3.77	5	0.1559	0.3932		-2	0	-1.6	40.02
c.41C>A	P14H 2D AIThe SynGAP1 missense variant P14H is listed in gnomAD (ID 6‑33420305‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome 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 further support a benign classification: 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 reported result for this variant, so its status is unavailable. Overall, the majority of predictions—including the high‑accuracy tools—indicate that P14H 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		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375								6-33420305-C-A			-3.747	Likely Benign	0.231	Likely Benign	Likely Benign										0.171	Likely Benign	-0.27	Neutral	0.742	Possibly Damaging	0.091	Benign	4.15	Benign	0.00	Affected	4.32	1	0.1999	0.5176		-2	0	-1.6	40.02
c.443C>A	P148H 2D AIThe SynGAP1 missense variant P148H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P148H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-11.034	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-3.21	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.90	Benign	0.00	Affected			0.1881	0.3847		0	-2	-1.6	40.02
c.482C>A	P161H 2D AIThe SynGAP1 missense variant P161H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that P161H is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-12.103	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.291	Likely Benign	-4.22	Deleterious	0.964	Probably Damaging	0.650	Possibly Damaging	3.89	Benign	0.00	Affected			0.2060	0.4039		0	-2	-1.6	40.02
c.566C>A	P189H 2D AIThe SynGAP1 missense variant P189H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P189H is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-9.633	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.298	Likely Benign	-6.49	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	4.00	Benign	0.00	Affected			0.1620	0.5327		0	-2	-1.6	40.02
c.59C>A	P20H 2D AIThe SynGAP1 missense variant P20H is reported in gnomAD (ID 6‑33420323‑C‑A) but has no ClinVar entry. Functional 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. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates benign. Foldetta results are unavailable. Overall, the preponderance of evidence from both consensus and high‑accuracy tools points to a benign effect for P20H, and this conclusion does not contradict any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.442804	Uncertain	0.448	0.899	0.500								6-33420323-C-A			-4.450	Likely Benign	0.352	Ambiguous	Likely Benign										0.132	Likely Benign	-0.69	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	4.23	Benign	0.00	Affected	4.32	1	0.1834	0.5066		-2	0	-1.6	40.02
c.755C>A	P252H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P252H missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the remaining evaluated algorithms (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. No other high‑confidence stability predictions are available. Overall, the preponderance of evidence indicates that P252H is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-11.991	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	0.2	1.96	Ambiguous	1.51	Ambiguous	0.82	Ambiguous	0.845	Likely Pathogenic	-8.27	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	5.76	Benign	0.00	Affected			0.1592	0.4128		0	-2	-1.6	40.02
c.80C>A	P27H 2D AIThe SynGAP1 missense variant P27H is not reported 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 P27H, 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		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-4.116	Likely Benign	0.177	Likely Benign	Likely Benign										0.128	Likely Benign	-2.46	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	3.79	Benign	0.00	Affected			0.2384	0.5290		0	-2	-1.6	40.02
c.824C>A	P275H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P275H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which classify the change as pathogenic. Tools that are inconclusive or uncertain are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Taken together, the majority of evidence points to a pathogenic impact, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250											-13.157	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous	2.34	Destabilizing	0.8	0.87	Ambiguous	1.61	Ambiguous	0.88	Ambiguous	0.585	Likely Pathogenic	-6.54	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.73	Pathogenic	0.01	Affected			0.2069	0.3074		0	-2	-1.6	40.02
c.827C>A	P276H 2D 3DClick to see structure in 3D Viewer AISynGAP1 P276H is reported in gnomAD (ID 6‑33437732‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic, while only AlphaMissense‑Optimized predicts a benign outcome. Uncertain results are provided by 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 pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250								6-33437732-C-A	1	6.20e-7	-10.469	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	1.98	Ambiguous	0.1	1.09	Ambiguous	1.54	Ambiguous	0.85	Ambiguous	0.534	Likely Pathogenic	-4.80	Deleterious	1.000	Probably Damaging	0.961	Probably Damaging	1.84	Pathogenic	0.00	Affected	3.38	19	0.1739	0.3439		-2	0	-1.6	40.02
c.893C>A	P298H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P298H 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 AlphaMissense‑Optimized. Those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Remaining tools (AlphaMissense‑Default, FoldX, Rosetta, Foldetta, premPS) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta is uncertain. Overall, the majority of predictions (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic interpretation. Therefore, the variant is most likely pathogenic, 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	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500											-9.777	Likely Pathogenic	0.443	Ambiguous	Likely Benign	1.57	Ambiguous	0.2	1.49	Ambiguous	1.53	Ambiguous	0.83	Ambiguous	0.313	Likely Benign	-2.37	Neutral	0.999	Probably Damaging	0.964	Probably Damaging	1.92	Pathogenic	0.04	Affected			0.1769	0.4943		0	-2	-1.6	40.02
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.1031G>T	G344V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G344V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only inconclusive result is premPS, which is listed as uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250											-14.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	13.33	Destabilizing	1.5	14.51	Destabilizing	13.92	Destabilizing	0.53	Ambiguous	0.889	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.48	Pathogenic	0.03	Affected			0.1244	0.4744		-1	-3	4.6	42.08
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.1109G>T	G370V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G370V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster into two groups: benign (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score of Likely Benign) and pathogenic (FoldX, Rosetta, Foldetta, and FATHMM). High‑accuracy assessments further refine this picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. Overall, the majority of evidence points toward a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.461924	Structured	0.434325	Uncertain	0.359	0.720	0.500											-5.328	Likely Benign	0.094	Likely Benign	Likely Benign	4.98	Destabilizing	3.8	5.61	Destabilizing	5.30	Destabilizing	-0.43	Likely Benign	0.427	Likely Benign	0.03	Neutral	0.000	Benign	0.000	Benign	1.32	Pathogenic	0.29	Tolerated			0.1306	0.4198		-1	-3	4.6	42.08
c.1115G>T	G372V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G372V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (variant ID 6-33438020-G-T). Functional prediction tools that agree on a benign effect include premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are REVEL, FoldX, Rosetta, FATHMM, and Foldetta. The high‑accuracy consensus from AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) indicates a pathogenic effect. Overall, the majority of predictions support a benign classification, and there is no conflict with ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.433034	Structured	0.430335	Uncertain	0.322	0.774	0.375								6-33438020-G-T			-5.898	Likely Benign	0.126	Likely Benign	Likely Benign	2.81	Destabilizing	0.3	2.91	Destabilizing	2.86	Destabilizing	0.02	Likely Benign	0.535	Likely Pathogenic	-0.92	Neutral	0.003	Benign	0.000	Benign	-0.74	Pathogenic	0.06	Tolerated	3.52	18	0.1663	0.4198		-3	-1	4.6	42.08
c.1118G>T	G373V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G373V is listed in ClinVar with an uncertain significance and is present in gnomAD (variant ID 6‑33438023‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are FoldX, Foldetta, and SIFT, while Rosetta is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as pathogenic. Overall, the majority of predictions support a benign impact, and this consensus does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625					Uncertain		1	6-33438023-G-T	6	5.03e-6	-6.062	Likely Benign	0.112	Likely Benign	Likely Benign	5.32	Destabilizing	3.2	0.82	Ambiguous	3.07	Destabilizing	0.09	Likely Benign	0.428	Likely Benign	-0.98	Neutral	0.007	Benign	0.001	Benign	3.90	Benign	0.00	Affected	3.53	16	0.1424	0.4004		-1	-3	4.6	42.08	207.6	-68.1	1.9	1.1	-0.6	0.1								Uncertain	Gly373 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364, res. Ala399-Ile411). Because the Ω loop is assumed to directly interact with the membrane, it moves arbitrarily throughout the WT solvent simulations. The Ω loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play major roles in protein functions that require flexibility, and thus hydrophobic residues like valine are rarely tolerated. Although no negative structural effects are observed in the variant simulations, Val373 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effect on the Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.1124G>T	G375V 2D AIThe SynGAP1 missense variant G375V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions (premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score of Likely Benign) and pathogenic predictions (REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, and FATHMM). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also benign, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a pathogenic effect. No prediction is missing or inconclusive. Overall, the majority of tools and the consensus score suggest a benign effect, but the Foldetta result introduces uncertainty. 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	C2	0.604312	Disordered	0.428340	Uncertain	0.301	0.836	0.625											-6.149	Likely Benign	0.149	Likely Benign	Likely Benign	3.93	Destabilizing	3.5	7.55	Destabilizing	5.74	Destabilizing	0.02	Likely Benign	0.547	Likely Pathogenic	-0.92	Neutral	0.845	Possibly Damaging	0.186	Benign	1.32	Pathogenic	0.06	Tolerated			0.1653	0.4193		-1	-3	4.6	42.08
c.1127G>T	G376V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G376V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, matching the majority of individual benign calls. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, SGM Consensus predicts benign, whereas Foldetta (integrating FoldX‑MD and Rosetta) predicts pathogenic. No prediction is missing or inconclusive. Overall, the balance of evidence leans toward a benign effect; this is consistent with the lack of ClinVar annotation and gnomAD presence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625											-6.242	Likely Benign	0.120	Likely Benign	Likely Benign	4.84	Destabilizing	0.8	-0.81	Ambiguous	2.02	Destabilizing	-0.18	Likely Benign	0.541	Likely Pathogenic	-0.66	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1594	0.3525		-1	-3	4.6	42.08
c.1133G>T	G378V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G378V is catalogued in gnomAD (ID 6‑33438038‑G‑T) but has no ClinVar submission. Functional prediction tools split in their assessment: benign calls come from premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls arise from REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy analyses further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts pathogenic. Overall, the balance of evidence, especially from the high‑accuracy tools, points to a benign effect for G378V, and this conclusion does not conflict with ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625								6-33438038-G-T	1	6.97e-7	-6.837	Likely Benign	0.168	Likely Benign	Likely Benign	12.88	Destabilizing	5.0	21.64	Destabilizing	17.26	Destabilizing	0.04	Likely Benign	0.606	Likely Pathogenic	-0.98	Neutral	1.000	Probably Damaging	0.994	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	12	0.1686	0.3708		-3	-1	4.6	42.08
c.1139G>T	G380V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G380V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions are reported by REVEL, FoldX, polyPhen‑2 HumDiv, and SIFT; Rosetta is uncertain. The SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority of the four high‑accuracy tools) is benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a pathogenic impact. Overall, the majority of evidence points to a benign effect, and this does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.724957	Disordered	0.432982	Uncertain	0.316	0.939	0.750											-6.234	Likely Benign	0.172	Likely Benign	Likely Benign	7.60	Destabilizing	2.5	1.75	Ambiguous	4.68	Destabilizing	-0.17	Likely Benign	0.574	Likely Pathogenic	-0.70	Neutral	0.816	Possibly Damaging	0.210	Benign	2.54	Benign	0.02	Affected			0.1618	0.3708		-1	-3	4.6	42.08
c.1142G>T	G381V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G381V is listed in ClinVar with an uncertain significance (ClinVar ID 1940172.0) and is present in the gnomAD database (6‑33438047‑G‑T). Functional prediction tools that report a benign effect include premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, FoldX, Rosetta, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority‑benign vote and is reported 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 pathogenic. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750					Uncertain		1	6-33438047-G-T	2	1.25e-6	-5.967	Likely Benign	0.146	Likely Benign	Likely Benign	7.16	Destabilizing	1.0	4.10	Destabilizing	5.63	Destabilizing	-0.32	Likely Benign	0.618	Likely Pathogenic	-0.95	Neutral	0.386	Benign	0.157	Benign	1.32	Pathogenic	0.10	Tolerated	4.32	9	0.1621	0.3902		-1	-3	4.6	42.08	214.6	-68.8	0.3	0.7	-0.5	0.3								Uncertain	Gly381 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364, res. Ala399-Ile411). Because the Ω loop is assumed to directly interact with the membrane, it moves arbitrarily throughout the WT solvent simulations. The Ω loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play major roles in protein functions that require flexibility, and thus hydrophobic residues like valine are rarely tolerated. Although no negative structural effects are observed in the variant simulations, Val381 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effects on Gly-rich Ω loop dynamics can only be well studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.1145G>T	G382V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G382V has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split opinion: benign predictions come from PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while premPS is uncertain. High‑accuracy assessments give a mixed signal: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, but Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy Foldetta result supports this. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750											-5.988	Likely Benign	0.155	Likely Benign	Likely Benign	6.40	Destabilizing	1.6	9.28	Destabilizing	7.84	Destabilizing	-0.53	Ambiguous	0.571	Likely Pathogenic	-0.54	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.03	Affected			0.1631	0.3708		-1	-3	4.6	42.08
c.1148G>T	G383V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G383V is not 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, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are FoldX, Rosetta, polyPhen‑2 HumDiv, and SIFT. 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 pathogenic. Overall, the majority of predictions lean toward a benign impact, 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.	Likely Benign	C2	0.728858	Disordered	0.429104	Uncertain	0.296	0.949	0.750											-5.769	Likely Benign	0.145	Likely Benign	Likely Benign	5.13	Destabilizing	2.1	4.06	Destabilizing	4.60	Destabilizing	-0.26	Likely Benign	0.406	Likely Benign	-0.72	Neutral	0.668	Possibly Damaging	0.207	Benign	4.12	Benign	0.01	Affected			0.1597	0.3493		-1	-3	4.6	42.08
c.1151G>T	G384V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G384V is catalogued in gnomAD (ID 6‑33438056‑G‑T) but has no entry in ClinVar. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect on protein stability. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750								6-33438056-G-T			-6.968	Likely Benign	0.131	Likely Benign	Likely Benign	3.69	Destabilizing	0.4	6.77	Destabilizing	5.23	Destabilizing	-0.11	Likely Benign	0.460	Likely Benign	-1.01	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.01	Affected	4.32	2	0.1599	0.3708		-3	-1	4.6	42.08
c.1157G>T	G386V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G386V is reported in gnomAD (6-33438062‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), and SIFT. 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, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign classification, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750								6-33438062-G-T			-6.405	Likely Benign	0.187	Likely Benign	Likely Benign	4.88	Destabilizing	3.0	5.09	Destabilizing	4.99	Destabilizing	-0.17	Likely Benign	0.458	Likely Benign	-0.64	Neutral	0.985	Probably Damaging	0.720	Possibly Damaging	3.91	Benign	0.01	Affected	4.32	3	0.1685	0.4189		-3	-1	4.6	42.08
c.1160G>T	G387V 2D 3DClick to see structure in 3D Viewer AISynGAP1 G387V is listed in ClinVar with an uncertain significance and is present in gnomAD (variant ID 6-33438065-G-T). Functional prediction tools that report a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as likely benign, while the Foldetta stability assessment (combining FoldX‑MD and Rosetta) indicates a pathogenic change. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as pathogenic. Overall, the majority of predictions favor a benign impact, and this consensus does not contradict the ClinVar uncertain status; thus the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.642678	Disordered	0.422910	Uncertain	0.293	0.861	0.750					Uncertain		1	6-33438065-G-T	22	1.37e-5	-6.199	Likely Benign	0.153	Likely Benign	Likely Benign	5.13	Destabilizing	1.8	6.44	Destabilizing	5.79	Destabilizing	-0.33	Likely Benign	0.390	Likely Benign	-0.54	Neutral	0.069	Benign	0.077	Benign	1.32	Pathogenic	0.01	Affected	4.32	3	0.1586	0.3708		-1	-3	4.6	42.08	207.7	-68.4	-0.7	0.8	-0.5	0.1								Uncertain	Gly387 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364 and res. Ala399-Ile411). The Ω loop is assumed to directly interact with the membrane, and it is observed to move arbitrarily throughout the WT solvent simulations. This loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play significant roles in protein functions that require flexibility, and thus hydrophobic residues like valine are rarely tolerated. Although no negative structural effects are visualized in the variant’s simulations, Val387 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. Since the effects on the Gly-rich Ω loop dynamics can only be well studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.1163G>T	G388V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388V is catalogued in gnomAD (6-33438068-G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign, whereas Foldetta—combining FoldX‑MD and Rosetta stability outputs—labels the variant as pathogenic. Overall, the majority of tools and the Foldetta result point to a pathogenic effect. This conclusion does not conflict with ClinVar, which currently contains no classification for G388V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750								6-33438068-G-T			-6.887	Likely Benign	0.120	Likely Benign	Likely Benign	6.58	Destabilizing	6.6	5.51	Destabilizing	6.05	Destabilizing	-0.11	Likely Benign	0.620	Likely Pathogenic	-0.93	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.01	Affected	4.32	3	0.1600	0.3897		-3	-1	4.6	42.08
c.1169G>T	G390V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G390V has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, FoldX, Rosetta, Foldetta, SIFT, and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default (benign), ESM1b (uncertain), FATHMM (pathogenic), and PROVEAN (benign), also yields a benign verdict; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, indicates pathogenic. With two high‑accuracy tools supporting benign and one supporting pathogenic, the overall evidence leans toward a benign effect. This conclusion does not contradict ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.626927	Disordered	0.413274	Uncertain	0.304	0.763	0.875											-7.137	In-Between	0.146	Likely Benign	Likely Benign	3.74	Destabilizing	0.6	4.88	Destabilizing	4.31	Destabilizing	-0.16	Likely Benign	0.509	Likely Pathogenic	-0.88	Neutral	0.002	Benign	0.002	Benign	1.32	Pathogenic	0.01	Affected			0.1537	0.4004		-1	-3	4.6	42.08
c.1172G>T	G391V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G391V is listed in ClinVar as Benign (ClinVar ID 1014488.0) and is present in gnomAD (variant ID 6‑33438077‑G‑T). Prediction tools that classify the variant as benign include premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. Tools that predict pathogenicity are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With two high‑accuracy tools supporting benign and one supporting pathogenic, the overall prediction leans toward a benign effect. This conclusion aligns with the ClinVar benign classification, so there is no contradiction with the existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750					Likely Benign		1	6-33438077-G-T	3	1.86e-6	-6.642	Likely Benign	0.133	Likely Benign	Likely Benign	4.23	Destabilizing	1.3	4.81	Destabilizing	4.52	Destabilizing	-0.11	Likely Benign	0.595	Likely Pathogenic	-0.98	Neutral	0.994	Probably Damaging	0.887	Possibly Damaging	1.32	Pathogenic	0.10	Tolerated	3.69	8	0.1621	0.3821		-1	-3	4.6	42.08	228.6	-69.0	0.0	0.8	-0.5	0.3								Uncertain	Gly387 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364 and res. Ala399-Ile411). The Ω loop is assumed to directly interact with the membrane, and it is observed to move arbitrarily throughout the WT solvent simulations. This loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play significant roles in protein functions that require flexibility, and thus hydrophobic residues like valine are rarely tolerated. Although no negative structural effects are visualized in the variant’s simulations, Val391 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. Since the effects on the Gly-rich Ω loop dynamics can only be well studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.1178G>T	G393V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G393V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Rosetta is uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while Foldetta predicts pathogenic. The SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑vs‑2 split. Overall, the majority of evidence (8 pathogenic vs. 4 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.		C2	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625											-6.358	Likely Benign	0.154	Likely Benign	Likely Benign	5.56	Destabilizing	2.3	-0.72	Ambiguous	2.42	Destabilizing	-0.01	Likely Benign	0.639	Likely Pathogenic	-2.69	Deleterious	0.982	Probably Damaging	0.648	Possibly Damaging	1.32	Pathogenic	0.01	Affected			0.1712	0.4144		-1	-3	4.6	42.08
c.1184G>T	G395V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G395V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only FoldX and SIFT predict pathogenic. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and the Foldetta stability analysis is uncertain. Taken together, the preponderance of evidence points to a benign impact for G395V, 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	0.513880	Disordered	0.396199	Uncertain	0.474	0.601	0.500											-5.617	Likely Benign	0.125	Likely Benign	Likely Benign	2.83	Destabilizing	0.7	-0.37	Likely Benign	1.23	Ambiguous	0.08	Likely Benign	0.288	Likely Benign	-1.49	Neutral	0.000	Benign	0.000	Benign	4.21	Benign	0.03	Affected			0.1290	0.4183		-1	-3	4.6	42.08
c.1187G>T	G396V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G396V is catalogued in gnomAD (6‑33438092‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, Rosetta, Foldetta, and PROVEAN. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect. Overall, the majority of predictions lean toward a benign impact, and this consensus does not contradict any ClinVar status (none reported). Thus, based on the available computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500								6-33438092-G-T	6	3.72e-6	-5.663	Likely Benign	0.120	Likely Benign	Likely Benign	3.49	Destabilizing	1.7	5.28	Destabilizing	4.39	Destabilizing	0.34	Likely Benign	0.332	Likely Benign	-2.56	Deleterious	0.062	Benign	0.014	Benign	3.90	Benign	0.24	Tolerated	3.41	15	0.1287	0.4337		-3	-1	4.6	42.08
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.1328G>T	G443V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Overall, the majority of evidence points to a benign impact for G443V, 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	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-4.130	Likely Benign	0.274	Likely Benign	Likely Benign	0.17	Likely Benign	0.2	-2.19	Stabilizing	-1.01	Ambiguous	0.21	Likely Benign	0.099	Likely Benign	-2.90	Deleterious	0.585	Possibly Damaging	0.195	Benign	3.36	Benign	0.12	Tolerated			0.1089	0.3375		-1	-3	4.6	42.08
c.1376G>T	G459V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G459V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; premPS is inconclusive and therefore not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the consensus of these predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for G459V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-13.606	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.79	Destabilizing	0.1	5.01	Destabilizing	4.40	Destabilizing	0.71	Ambiguous	0.605	Likely Pathogenic	-8.46	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.99	Benign	0.00	Affected			0.0997	0.4240		-1	-3	4.6	42.08
c.1505G>T	G502V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: all evaluated algorithms except premPS (which predicts benign) classify the substitution as pathogenic or likely pathogenic. The consensus of high‑accuracy predictors is consistent: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a destabilizing, pathogenic outcome. In contrast, premPS is the sole tool suggesting a benign impact. Overall, the overwhelming majority of evidence points to a pathogenic effect for G502V, and this conclusion does not conflict with the absence of a ClinVar classification. Thus, the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000											-15.278	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	3.56	Destabilizing	1.0	5.50	Destabilizing	4.53	Destabilizing	0.43	Likely Benign	0.917	Likely Pathogenic	-8.65	Deleterious	0.999	Probably Damaging	0.944	Probably Damaging	-1.67	Pathogenic	0.00	Affected			0.1406	0.3387		-1	-3	4.6	42.08
c.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.158G>T	G53V 2D AIThe SynGAP1 missense variant G53V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.308	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.238	Likely Benign	-1.71	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.11	Benign	0.00	Affected			0.1193	0.4833		-1	-3	4.6	42.08
c.1739G>T	G580V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. The only inconclusive result is premPS, which is listed as uncertain. No tool predicts a benign effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenic. 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 any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-13.705	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.10	Destabilizing	0.1	3.89	Destabilizing	4.00	Destabilizing	0.79	Ambiguous	0.750	Likely Pathogenic	-8.66	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.18	Pathogenic	0.04	Affected			0.1270	0.2909		-1	-3	4.6	42.08
c.1826G>T	G609V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS and AlphaMissense‑Optimized, whereas the remaining 10 tools (SGM Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM) all predict pathogenicity. High‑accuracy assessments further highlight the discordance: AlphaMissense‑Optimized reports a benign effect, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate pathogenicity. With the majority of evidence pointing to deleterious impact, 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	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000											-11.049	Likely Pathogenic	0.374	Ambiguous	Likely Benign	4.17	Destabilizing	0.3	3.77	Destabilizing	3.97	Destabilizing	0.34	Likely Benign	0.734	Likely Pathogenic	-4.47	Deleterious	0.974	Probably Damaging	0.818	Possibly Damaging	-1.48	Pathogenic	0.02	Affected			0.1269	0.3317		-1	-3	4.6	42.08
c.1940G>T	G647V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact uniformly classify the substitution as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a tolerated change. No tool predicts pathogenicity; only FoldX and Rosetta report uncertain stability effects, which are treated as unavailable evidence. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. Therefore, 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	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-4.713	Likely Benign	0.126	Likely Benign	Likely Benign	0.85	Ambiguous	0.1	-0.59	Ambiguous	0.13	Likely Benign	-0.13	Likely Benign	0.115	Likely Benign	-1.77	Neutral	0.178	Benign	0.073	Benign	3.52	Benign	0.12	Tolerated			0.1318	0.3946		-1	-3	4.6	42.08
c.1973G>T	G658V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv; Rosetta’s output is uncertain and therefore not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Taken together, the majority of reliable predictors indicate a benign impact. Thus, 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	GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-6.815	Likely Benign	0.166	Likely Benign	Likely Benign	-0.07	Likely Benign	0.0	-0.71	Ambiguous	-0.39	Likely Benign	0.34	Likely Benign	0.117	Likely Benign	-3.23	Deleterious	0.841	Possibly Damaging	0.264	Benign	3.38	Benign	0.13	Tolerated			0.1337	0.3330		-1	-3	4.6	42.08
c.2042G>T	G681V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus predicts a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. No other high‑confidence predictions are available. Taken together, the consensus of pathogenic predictions outweighs the single benign call, indicating that G681V is most likely pathogenic. This assessment is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-14.043	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	3.21	Destabilizing	2.0	6.12	Destabilizing	4.67	Destabilizing	0.64	Ambiguous	0.572	Likely Pathogenic	-8.98	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	3.33	Benign	0.01	Affected			0.1350	0.3840		-1	-3	4.6	42.08
c.2057G>T	G686V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686V has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on benign impact are Rosetta and FATHMM, while the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) indicate a pathogenic effect. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for G686V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-13.751	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.89	Ambiguous	0.5	0.21	Likely Benign	0.55	Ambiguous	0.74	Ambiguous	0.570	Likely Pathogenic	-8.08	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.01	Affected			0.1059	0.3646		-1	-3	4.6	42.08
c.2135G>T	G712V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while 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 report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. 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	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-10.466	Likely Pathogenic	0.877	Likely Pathogenic	Ambiguous	3.79	Destabilizing	0.0	6.18	Destabilizing	4.99	Destabilizing	0.79	Ambiguous	0.410	Likely Benign	-7.55	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.00	Affected			0.1395	0.3712		-1	-3	4.6	42.08
c.2249G>T	G750V 2D AIThe SynGAP1 missense variant G750V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore show AlphaMissense‑Optimized as benign, while the remaining high‑confidence tools (PROVEAN, polyPhen‑2, SIFT, FATHMM) all indicate pathogenicity. Overall, the majority of evidence (five pathogenic vs four benign) points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.618285	Disordered	0.646832	Binding	0.348	0.866	0.625											-4.512	Likely Benign	0.134	Likely Benign	Likely Benign										0.145	Likely Benign	-2.54	Deleterious	0.984	Probably Damaging	0.850	Possibly Damaging	2.45	Pathogenic	0.01	Affected			0.1270	0.4212		-1	-3	4.6	42.08
c.2270G>T	G757V 2D AIThe SynGAP1 missense variant G757V is not reported 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 variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.830995	Binding	0.310	0.869	0.375											-4.840	Likely Benign	0.149	Likely Benign	Likely Benign										0.087	Likely Benign	-1.47	Neutral	0.801	Possibly Damaging	0.494	Possibly Damaging	2.68	Benign	0.07	Tolerated			0.1089	0.3512		-1	-3	4.6	42.08
c.2327G>T	G776V 2D AIThe SynGAP1 missense variant G776V is listed in gnomAD (ID 6‑33442485‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also indicates a likely benign outcome; Foldetta data are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442485-G-T			-6.541	Likely Benign	0.515	Ambiguous	Likely Benign										0.180	Likely Benign	-2.25	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	4.19	Benign	0.01	Affected	3.64	6	0.0993	0.4223		-3	-1	4.6	42.08
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.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.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.2543G>T	G848V 2D AIThe SynGAP1 missense variant G848V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443095‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500								6-33443095-G-T	1	6.20e-7	-4.445	Likely Benign	0.255	Likely Benign	Likely Benign										0.218	Likely Benign	-1.39	Neutral	0.977	Probably Damaging	0.856	Possibly Damaging	2.57	Benign	0.02	Affected	4.32	4	0.1184	0.4336		-3	-1	4.6	42.08
c.2549G>T	G850V 2D AIThe SynGAP1 missense variant G850V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools converge on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G850V, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500											-5.379	Likely Benign	0.081	Likely Benign	Likely Benign										0.213	Likely Benign	-1.74	Neutral	0.960	Probably Damaging	0.679	Possibly Damaging	4.21	Benign	0.02	Affected			0.1255	0.4077		-1	-3	4.6	42.08
c.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.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.2600G>T	G867V 2D AIThe SynGAP1 missense variant G867V is not 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 and polyPhen‑2 HumVar. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split between benign and uncertain calls. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (five benign predictions versus two pathogenic predictions, with no decisive high‑accuracy support for pathogenicity) indicates that 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.			0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250											-7.049	In-Between	0.441	Ambiguous	Likely Benign										0.111	Likely Benign	-2.23	Neutral	0.999	Probably Damaging	0.958	Probably Damaging	2.70	Benign	0.10	Tolerated			0.1125	0.4613		-1	-3	4.6	42.08
c.2645G>T	G882V 2D AIThe SynGAP1 missense variant G882V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this 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		0.690604	Disordered	0.632888	Binding	0.306	0.878	0.250											-5.893	Likely Benign	0.257	Likely Benign	Likely Benign										0.115	Likely Benign	-2.41	Neutral	0.224	Benign	0.066	Benign	2.06	Pathogenic	0.02	Affected			0.1178	0.4717		-1	-3	4.6	42.08
c.2666G>T	G889V 2D AIThe SynGAP1 missense variant G889V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G889V, 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		0.690604	Disordered	0.552581	Binding	0.331	0.928	0.625											-5.781	Likely Benign	0.148	Likely Benign	Likely Benign										0.101	Likely Benign	-2.11	Neutral	0.611	Possibly Damaging	0.243	Benign	2.39	Pathogenic	0.03	Affected			0.1198	0.4523		-1	-3	4.6	42.08
c.2681G>T	G894V 2D AIThe SynGAP1 missense variant G894V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with the ClinVar status. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750											-5.047	Likely Benign	0.395	Ambiguous	Likely Benign										0.188	Likely Benign	-2.61	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.64	Benign	0.02	Affected			0.1187	0.4091		-1	-3	4.6	42.08
c.2687G>T	G896V 2D AIThe SynGAP1 missense variant G896V is reported in gnomAD (6-33443239-G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign outcome. Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect for G896V, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625								6-33443239-G-T	1	6.20e-7	-2.936	Likely Benign	0.285	Likely Benign	Likely Benign										0.165	Likely Benign	-1.96	Neutral	0.997	Probably Damaging	0.912	Probably Damaging	2.46	Pathogenic	0.30	Tolerated	4.32	4	0.1264	0.4026		-3	-1	4.6	42.08
c.2708G>T	G903V 2D AIThe SynGAP1 missense variant G903V is not reported 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 AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the balance of evidence (five benign predictions versus three pathogenic predictions, with no conflicting ClinVar annotation) indicates that the variant is most likely benign. This conclusion does not contradict any ClinVar status, as the variant is not currently catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375											-4.750	Likely Benign	0.491	Ambiguous	Likely Benign										0.168	Likely Benign	-1.93	Neutral	0.997	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.95	Tolerated			0.1269	0.4266		-1	-3	4.6	42.08
c.2729G>T	G910V 2D AIThe SynGAP1 missense variant G910V is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443281‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. 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 results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. This prediction 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.			0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250								6-33443281-G-T	1	6.20e-7	-4.362	Likely Benign	0.724	Likely Pathogenic	Likely Benign										0.237	Likely Benign	-2.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.73	Benign	0.02	Affected	3.77	5	0.1179	0.3662		-3	-1	4.6	42.08
c.2744G>T	G915V 2D AIThe SynGAP1 missense variant G915V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (6‑33443296‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign; the Foldetta stability analysis is unavailable. Overall, the majority of predictions, including the most reliable tools, indicate a benign impact. This consensus does not contradict ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.808641	Binding	0.302	0.880	0.375								6-33443296-G-T			-4.586	Likely Benign	0.189	Likely Benign	Likely Benign										0.149	Likely Benign	-2.52	Deleterious	0.997	Probably Damaging	0.918	Probably Damaging	2.68	Benign	0.01	Affected	3.77	5	0.0927	0.4291		-3	-1	4.6	42.08
c.275G>T	G92V 2D AIThe SynGAP1 missense variant G92V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, 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 further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact for G92V, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.537848	Binding	0.337	0.874	0.625											-4.627	Likely Benign	0.338	Likely Benign	Likely Benign										0.164	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.972	Probably Damaging	4.00	Benign	0.00	Affected			0.1171	0.4363		-1	-3	4.6	42.08
c.2813G>T	G938V 2D AIThe SynGAP1 missense variant G938V is not reported 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 result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that G938V 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		0.905695	Disordered	0.949795	Binding	0.318	0.883	0.625											-6.112	Likely Benign	0.153	Likely Benign	Likely Benign										0.123	Likely Benign	-0.81	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.83	Benign	0.31	Tolerated			0.1230	0.3811		-1	-3	4.6	42.08
c.2819G>T	G940V 2D AIThe SynGAP1 missense variant G940V 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 further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625											-6.252	Likely Benign	0.078	Likely Benign	Likely Benign										0.110	Likely Benign	0.36	Neutral	0.626	Possibly Damaging	0.419	Benign	2.92	Benign	0.31	Tolerated			0.1222	0.3822		-1	-3	4.6	42.08
c.2828G>T	G943V 2D AIThe SynGAP1 missense variant G943V 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 substitution as benign. The only tool with an uncertain outcome is ESM1b, which does not alter the overall consensus. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign classification. High‑accuracy predictors corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are not available. Taken together, the evidence overwhelmingly supports a benign interpretation, and there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.973328	Disordered	0.860437	Binding	0.372	0.910	0.750											-7.658	In-Between	0.092	Likely Benign	Likely Benign										0.265	Likely Benign	-0.43	Neutral	0.224	Benign	0.062	Benign	2.85	Benign	0.16	Tolerated			0.1399	0.3507		-1	-3	4.6	42.08
c.2831G>T	G944V 2D AIThe SynGAP1 missense variant G944V is catalogued in gnomAD (ID 6‑33443383‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the substitution as benign or likely benign. Only SIFT predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments confirm the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus likewise indicates a likely benign status. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the collective evidence points to a benign variant, 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 its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750								6-33443383-G-T	1	6.20e-7	-7.536	In-Between	0.090	Likely Benign	Likely Benign										0.446	Likely Benign	-1.41	Neutral	0.126	Benign	0.096	Benign	3.70	Benign	0.00	Affected	4.32	4	0.1455	0.3507		-3	-1	4.6	42.08
c.2837G>T	G946V 2D AIThe SynGAP1 missense variant G946V is not reported 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 G946V, 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		0.985417	Disordered	0.845792	Binding	0.357	0.920	0.750											-7.528	In-Between	0.109	Likely Benign	Likely Benign										0.368	Likely Benign	-0.30	Neutral	0.901	Possibly Damaging	0.516	Possibly Damaging	4.57	Benign	0.00	Affected			0.1524	0.3707		-1	-3	4.6	42.08
c.2840G>T	G947V 2D AIThe SynGAP1 missense variant G947V 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign, whereas polyPhen‑2 HumDiv and SIFT predict pathogenicity; ESM1b remains uncertain. High‑accuracy methods reinforce the benign assessment: AlphaMissense‑Optimized scores benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and Foldetta data are not available. Overall, the preponderance of evidence points to a benign impact for G947V, 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		0.988695	Disordered	0.850554	Binding	0.358	0.919	0.750											-7.171	In-Between	0.105	Likely Benign	Likely Benign										0.296	Likely Benign	-1.11	Neutral	0.586	Possibly Damaging	0.303	Benign	4.93	Benign	0.01	Affected			0.1443	0.3507		-1	-3	4.6	42.08
c.2843G>T	G948V 2D AIThe SynGAP1 missense variant G948V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. 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 G948V 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		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750											-6.541	Likely Benign	0.102	Likely Benign	Likely Benign										0.256	Likely Benign	-0.48	Neutral	0.901	Possibly Damaging	0.435	Benign	4.52	Benign	0.06	Tolerated			0.1464	0.3507		-1	-3	4.6	42.08
c.2846G>T	G949V 2D AIThe SynGAP1 missense variant G949V is not 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, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. 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.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750											-7.364	In-Between	0.102	Likely Benign	Likely Benign										0.328	Likely Benign	-0.55	Neutral	0.992	Probably Damaging	0.834	Possibly Damaging	2.21	Pathogenic	0.01	Affected			0.1493	0.3165		-1	-3	4.6	42.08
c.2849G>T	G950V 2D AIThe SynGAP1 missense variant G950V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that G950V is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.888649	Binding	0.368	0.923	0.750											-7.796	In-Between	0.093	Likely Benign	Likely Benign										0.428	Likely Benign	-0.91	Neutral	0.411	Benign	0.239	Benign	2.26	Pathogenic	0.01	Affected			0.1392	0.3507		-1	-3	4.6	42.08
c.2855G>T	G952V 2D AIThe SynGAP1 missense variant G952V is listed in ClinVar (ID 2055482.0) 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), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b 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 is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that G952V is most likely benign, and this conclusion does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.910621	Binding	0.341	0.926	0.750					Uncertain		1				-7.074	In-Between	0.078	Likely Benign	Likely Benign										0.231	Likely Benign	-0.33	Neutral	0.000	Benign	0.000	Benign	3.20	Benign	0.02	Affected	3.77	5	0.1538	0.3507		-1	-3	4.6	42.08
c.287G>T	G96V 2D AIThe SynGAP1 missense variant G96V is not reported 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		0.657645	Disordered	0.599491	Binding	0.335	0.871	0.625											-4.266	Likely Benign	0.078	Likely Benign	Likely Benign										0.109	Likely Benign	-1.43	Neutral	0.334	Benign	0.029	Benign	4.18	Benign	0.00	Affected			0.1575	0.3833		-1	-3	4.6	42.08
c.2903G>T	G968V 2D AIThe SynGAP1 missense variant G968V is not reported 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 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		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750											-6.152	Likely Benign	0.093	Likely Benign	Likely Benign										0.239	Likely Benign	-1.08	Neutral	0.918	Possibly Damaging	0.525	Possibly Damaging	4.19	Benign	0.11	Tolerated			0.1252	0.4036		-1	-3	4.6	42.08
c.2906G>T	G969V 2D AIThe SynGAP1 missense variant G969V is not reported 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		0.950334	Disordered	0.956572	Binding	0.405	0.898	0.750											-5.946	Likely Benign	0.089	Likely Benign	Likely Benign										0.116	Likely Benign	-0.92	Neutral	0.761	Possibly Damaging	0.239	Benign	4.18	Benign	0.01	Affected			0.1497	0.3847		-1	-3	4.6	42.08
c.2918G>T	G973V 2D AIThe SynGAP1 missense variant G973V 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 as pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification. Foldetta results are unavailable, so they do not influence the assessment. Overall, 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		0.887230	Disordered	0.959498	Binding	0.390	0.897	0.625											-4.688	Likely Benign	0.097	Likely Benign	Likely Benign										0.092	Likely Benign	-0.76	Neutral	0.224	Benign	0.091	Benign	4.18	Benign	0.01	Affected			0.1392	0.3684		-1	-3	4.6	42.08
c.2942G>T	G981V 2D AIThe SynGAP1 missense variant G981V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for G981V, 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		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625											-3.873	Likely Benign	0.714	Likely Pathogenic	Likely Benign										0.156	Likely Benign	-2.10	Neutral	0.997	Probably Damaging	0.958	Probably Damaging	3.75	Benign	0.00	Affected			0.1322	0.3861		-1	-3	4.6	42.08
c.2972G>T	G991V 2D AIThe SynGAP1 missense variant G991V is not reported 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		0.745909	Disordered	0.911393	Binding	0.286	0.920	0.750											-4.129	Likely Benign	0.098	Likely Benign	Likely Benign										0.064	Likely Benign	-1.61	Neutral	0.440	Benign	0.253	Benign	4.16	Benign	0.01	Affected			0.1148	0.3961		-1	-3	4.6	42.08
c.3032G>T	G1011V 2D AIThe SynGAP1 missense variant G1011V is not reported 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		0.834292	Disordered	0.898380	Binding	0.332	0.869	0.625											-4.883	Likely Benign	0.129	Likely Benign	Likely Benign										0.133	Likely Benign	-1.21	Neutral	0.473	Possibly Damaging	0.192	Benign	2.71	Benign	0.01	Affected			0.1352	0.3434		-1	-3	4.6	42.08
c.3041G>T	G1014V 2D AIThe SynGAP1 missense variant G1014V is listed in ClinVar (ID 809922.0) 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 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 further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.914808	Binding	0.293	0.835	0.625					Uncertain		1				-4.612	Likely Benign	0.181	Likely Benign	Likely Benign										0.053	Likely Benign	-2.47	Neutral	0.818	Possibly Damaging	0.377	Benign	2.72	Benign	0.06	Tolerated	3.77	5	0.1359	0.3533		-1	-3	4.6	42.08
c.308G>T	G103V 2D AIThe SynGAP1 missense variant G103V is not reported 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		0.795062	Disordered	0.687376	Binding	0.381	0.877	0.625											-3.584	Likely Benign	0.151	Likely Benign	Likely Benign										0.126	Likely Benign	-0.96	Neutral	0.820	Possibly Damaging	0.376	Benign	4.22	Benign	0.00	Affected			0.1420	0.3404		-1	-3	4.6	42.08
c.3119G>T	G1040V 2D AIThe SynGAP1 missense variant G1040V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443671‑G‑T). Prediction tools that agree on a benign effect are ESM1b and AlphaMissense‑Optimized; those that predict a pathogenic effect include REVEL, 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, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625					Uncertain		1	6-33443671-G-T	4	2.48e-6	-3.453	Likely Benign	0.645	Likely Pathogenic	Likely Benign										0.774	Likely Pathogenic	-2.89	Deleterious	0.827	Possibly Damaging	0.456	Possibly Damaging	-0.74	Pathogenic	0.01	Affected	3.77	5	0.1239	0.4213		-1	-3	4.6	42.08
c.3143G>T	G1048V 2D AIThe SynGAP1 missense variant G1048V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, 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. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.923876	Binding	0.346	0.916	0.750											-6.108	Likely Benign	0.079	Likely Benign	Likely Benign										0.520	Likely Pathogenic	-0.59	Neutral	0.958	Probably Damaging	0.787	Possibly Damaging	2.54	Benign	0.11	Tolerated			0.1312	0.3688		-1	-3	4.6	42.08
c.3149G>T	G1050V 2D AIThe SynGAP1 missense variant G1050V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for G1050V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.987317	Disordered	0.906802	Binding	0.370	0.928	0.875											-6.450	Likely Benign	0.108	Likely Benign	Likely Benign										0.066	Likely Benign	-0.83	Neutral	0.126	Benign	0.096	Benign	2.49	Pathogenic	0.13	Tolerated			0.1260	0.3684		-1	-3	4.6	42.08
c.3152G>T	G1051V 2D AIThe SynGAP1 missense variant G1051V is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443704‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for G1051V, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.900141	Binding	0.358	0.936	0.875								6-33443704-G-T	1	6.20e-7	-7.098	In-Between	0.102	Likely Benign	Likely Benign										0.460	Likely Benign	-0.62	Neutral	0.245	Benign	0.096	Benign	-0.74	Pathogenic	0.17	Tolerated	3.77	5	0.1274	0.3680		-3	-1	4.6	42.08
c.3155G>T	G1052V 2D AIThe SynGAP1 missense variant G1052V 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign, while the high‑accuracy AlphaMissense‑Optimized score is benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. In contrast, polyPhen‑2 HumDiv and HumVar both predict pathogenic, and ESM1b remains uncertain. No Foldetta stability assessment is available, so it does not influence the overall interpretation. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-7.717	In-Between	0.094	Likely Benign	Likely Benign										0.452	Likely Benign	-0.12	Neutral	0.901	Possibly Damaging	0.619	Possibly Damaging	3.90	Benign	0.19	Tolerated			0.1329	0.3499		-1	-3	4.6	42.08
c.3161G>T	G1054V 2D AIThe SynGAP1 missense variant G1054V 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 further support this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.983019	Disordered	0.878015	Binding	0.389	0.936	0.875											-6.994	Likely Benign	0.110	Likely Benign	Likely Benign										0.171	Likely Benign	-0.22	Neutral	0.818	Possibly Damaging	0.221	Benign	4.01	Benign	0.18	Tolerated			0.1578	0.3694		-1	-3	4.6	42.08
c.3164G>T	G1055V 2D AIThe SynGAP1 missense variant G1055V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while ESM1b 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875											-7.434	In-Between	0.114	Likely Benign	Likely Benign										0.399	Likely Benign	0.26	Neutral	0.818	Possibly Damaging	0.222	Benign	3.28	Benign	0.17	Tolerated			0.1399	0.3694		-1	-3	4.6	42.08
c.3167G>T	G1056V 2D AIThe SynGAP1 missense variant G1056V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (7 benign vs 2 pathogenic) supports a benign classification. This consensus does not contradict ClinVar status, which has no entry for this variant. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875											-8.130	Likely Pathogenic	0.097	Likely Benign	Likely Benign										0.448	Likely Benign	-0.24	Neutral	0.292	Benign	0.110	Benign	1.83	Pathogenic	0.08	Tolerated			0.1488	0.3507		-1	-3	4.6	42.08
c.3173G>T	G1058V 2D AIThe SynGAP1 missense variant G1058V is reported in gnomAD (variant ID 6‑33443725‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.980739	Disordered	0.885724	Binding	0.407	0.929	0.875								6-33443725-G-T	1	6.21e-7	-6.877	Likely Benign	0.114	Likely Benign	Likely Benign										0.152	Likely Benign	-0.12	Neutral	0.000	Benign	0.001	Benign	5.22	Benign	0.01	Affected	3.77	5	0.1561	0.3694		-3	-1	4.6	42.08
c.3176G>T	G1059V 2D AIThe SynGAP1 missense variant G1059V 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), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score benign, while the majority‑vote SGM‑Consensus also classifies it as likely benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy tools corroborate the benign prediction: AlphaMissense‑Optimized is benign and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign; Foldetta results are not available. Overall, the preponderance of evidence supports a benign classification for G1059V, and this assessment does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.983019	Disordered	0.898939	Binding	0.399	0.926	0.875											-7.242	In-Between	0.106	Likely Benign	Likely Benign										0.478	Likely Benign	-0.82	Neutral	0.259	Benign	0.066	Benign	2.54	Benign	0.00	Affected			0.1462	0.3494		-1	-3	4.6	42.08
c.3179G>T	G1060V 2D AIThe SynGAP1 missense variant G1060V is listed in ClinVar as benign (ClinVar ID 1345112.0) and is observed in gnomAD (6‑33443731‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign, and AlphaMissense‑Optimized also reports a benign outcome. No Foldetta stability assessment is available for this variant. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar designation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.979242	Disordered	0.913048	Binding	0.407	0.928	0.875					Benign		1	6-33443731-G-T	1	6.22e-7	-6.966	Likely Benign	0.103	Likely Benign	Likely Benign										0.369	Likely Benign	-0.73	Neutral	0.986	Probably Damaging	0.728	Possibly Damaging	2.63	Benign	0.33	Tolerated	4.32	2	0.1453	0.3494		-1	-3	4.6	42.08
c.3182G>T	G1061V 2D AIThe SynGAP1 missense variant G1061V is not reported 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. Overall, the majority of evidence indicates that G1061V 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		0.978672	Disordered	0.926729	Binding	0.394	0.923	0.875											-6.709	Likely Benign	0.106	Likely Benign	Likely Benign										0.307	Likely Benign	-1.41	Neutral	0.224	Benign	0.066	Benign	3.98	Benign	0.00	Affected			0.1431	0.3684		-1	-3	4.6	42.08
c.3185G>T	G1062V 2D AIThe SynGAP1 missense variant G1062V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this 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		0.976962	Disordered	0.936972	Binding	0.368	0.917	0.875											-6.598	Likely Benign	0.103	Likely Benign	Likely Benign										0.377	Likely Benign	-0.78	Neutral	0.259	Benign	0.066	Benign	4.12	Benign	0.01	Affected			0.1441	0.3694		-1	-3	4.6	42.08
c.3188G>T	G1063V 2D AIThe SynGAP1 missense variant G1063V is not reported 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (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 preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that G1063V is most likely benign, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.975134	Disordered	0.945784	Binding	0.394	0.913	0.875											-6.228	Likely Benign	0.083	Likely Benign	Likely Benign										0.045	Likely Benign	-0.82	Neutral	0.004	Benign	0.002	Benign	4.29	Benign	0.03	Affected			0.1434	0.3707		-1	-3	4.6	42.08
c.3212G>T	G1071V 2D AIThe SynGAP1 missense variant G1071V is catalogued in gnomAD (ID 6‑33443764‑G‑T) but has no ClinVar entry. In silico prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or likely 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 results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, supports a benign interpretation. This prediction does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983740	Binding	0.313	0.905	0.875								6-33443764-G-T	3	1.87e-6	-2.901	Likely Benign	0.300	Likely Benign	Likely Benign										0.110	Likely Benign	-2.42	Neutral	0.057	Benign	0.022	Benign	4.14	Benign	0.01	Affected	3.77	5	0.1408	0.3634		-3	-1	4.6	42.08
c.3266G>T	G1089V 2D AIThe SynGAP1 missense variant G1089V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for G1089V. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-4.809	Likely Benign	0.527	Ambiguous	Likely Benign										0.182	Likely Benign	-2.81	Deleterious	0.984	Probably Damaging	0.722	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.1326	0.4413		-1	-3	4.6	42.08
c.3299G>T	G1100V 2D AIThe SynGAP1 missense variant G1100V is reported in gnomAD (variant ID 6‑33443851‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign); pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the balance of evidence favors a benign classification for G1100V, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875								6-33443851-G-T	1	6.51e-7	-2.362	Likely Benign	0.118	Likely Benign	Likely Benign										0.198	Likely Benign	-2.43	Neutral	0.992	Probably Damaging	0.906	Possibly Damaging	1.93	Pathogenic	0.01	Affected	3.77	5	0.1297	0.4036		-3	-1	4.6	42.08
c.32G>T	G11V 2D AIThe SynGAP1 missense variant G11V is reported in gnomAD (variant ID 6‑33420296‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that G11V is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.501027	Binding	0.348	0.915	0.375								6-33420296-G-T			-4.079	Likely Benign	0.160	Likely Benign	Likely Benign										0.146	Likely Benign	-0.38	Neutral	0.668	Possibly Damaging	0.049	Benign	3.93	Benign	0.00	Affected	4.32	1	0.1292	0.4522		-3	-1	4.6	42.08
c.3338G>T	G1113V 2D AIThe SynGAP1 missense variant G1113V is not reported 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 variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875											-5.708	Likely Benign	0.093	Likely Benign	Likely Benign										0.088	Likely Benign	-1.98	Neutral	0.827	Possibly Damaging	0.456	Possibly Damaging	2.53	Benign	0.11	Tolerated			0.1333	0.4224		-1	-3	4.6	42.08
c.3347G>T	G1116V 2D AIThe SynGAP1 missense variant G1116V is reported in gnomAD (variant ID 6‑33443899‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.873279	Binding	0.320	0.909	0.750								6-33443899-G-T			-6.426	Likely Benign	0.102	Likely Benign	Likely Benign										0.393	Likely Benign	-0.79	Neutral	0.626	Possibly Damaging	0.375	Benign	4.06	Benign	0.06	Tolerated	4.32	2	0.1268	0.3494		-3	-1	4.6	42.08
c.3350G>T	G1117V 2D AIThe SynGAP1 missense variant G1117V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, 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		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750											-7.251	In-Between	0.083	Likely Benign	Likely Benign										0.284	Likely Benign	-1.32	Neutral	0.011	Benign	0.014	Benign	4.57	Benign	0.04	Affected			0.1312	0.3680		-1	-3	4.6	42.08
c.3356G>T	G1119V 2D AIThe SynGAP1 missense variant G1119V 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 two tools, polyPhen‑2 HumDiv and polyPhen‑2 HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion 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		0.827927	Disordered	0.818538	Binding	0.339	0.928	0.875											-6.428	Likely Benign	0.099	Likely Benign	Likely Benign										0.352	Likely Benign	-0.94	Neutral	0.918	Possibly Damaging	0.604	Possibly Damaging	3.91	Benign	0.31	Tolerated			0.1493	0.3707		-1	-3	4.6	42.08
c.3359G>T	G1120V 2D AIThe SynGAP1 missense variant G1120V is catalogued in gnomAD (6‑33443911‑G‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign, while ESM1b remains uncertain. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), classifies the variant as “Likely Benign.” AlphaMissense‑Optimized also reports a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875								6-33443911-G-T			-7.659	In-Between	0.081	Likely Benign	Likely Benign										0.355	Likely Benign	-1.20	Neutral	0.292	Benign	0.157	Benign	3.61	Benign	0.06	Tolerated	3.77	5	0.1360	0.3694		-3	-1	4.6	42.08
c.335G>T	G112V 2D AIThe SynGAP1 missense variant G112V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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		0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-2.411	Likely Benign	0.230	Likely Benign	Likely Benign										0.159	Likely Benign	-3.39	Deleterious	0.421	Benign	0.108	Benign	3.96	Benign	0.00	Affected			0.1225	0.4218		-1	-3	4.6	42.08
c.3365G>T	G1122V 2D AIThe SynGAP1 missense variant G1122V 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 return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875											-6.398	Likely Benign	0.088	Likely Benign	Likely Benign										0.271	Likely Benign	-1.18	Neutral	0.059	Benign	0.025	Benign	4.49	Benign	0.10	Tolerated			0.1381	0.3694		-1	-3	4.6	42.08
c.3368G>T	G1123V 2D AIThe SynGAP1 missense variant G1123V is not reported 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective predictions strongly suggest that G1123V 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		0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875											-7.129	In-Between	0.091	Likely Benign	Likely Benign										0.333	Likely Benign	-1.03	Neutral	0.292	Benign	0.157	Benign	4.35	Benign	0.29	Tolerated			0.1362	0.3694		-1	-3	4.6	42.08
c.3371G>T	G1124V 2D AIThe SynGAP1 missense variant G1124V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that G1124V is most likely benign, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.833401	Binding	0.341	0.931	0.875											-6.980	Likely Benign	0.094	Likely Benign	Likely Benign										0.315	Likely Benign	-0.96	Neutral	0.586	Possibly Damaging	0.172	Benign	4.75	Benign	0.00	Affected			0.1299	0.3888		-1	-3	4.6	42.08
c.3374G>T	G1125V 2D AIThe SynGAP1 missense variant G1125V is reported in gnomAD (variant ID 6-33443926-G-T) but has no ClinVar entry. Functional prediction tools cluster into two groups: six tools (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all predict a benign effect, whereas three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT) predict pathogenicity. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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 is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.835839	Binding	0.339	0.923	0.875								6-33443926-G-T			-6.776	Likely Benign	0.095	Likely Benign	Likely Benign										0.320	Likely Benign	-0.99	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	4.55	Benign	0.02	Affected	3.77	5	0.1407	0.3688		-3	-1	4.6	42.08
c.3377G>T	G1126V 2D AIThe SynGAP1 missense variant G1126V is listed in ClinVar with an uncertain significance and is present in the gnomAD database. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all classify the change as benign. Only the SIFT algorithm predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign, while Foldetta’s protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a benign variant, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.837209	Binding	0.345	0.918	0.875					Uncertain		1	6-33443929-G-T			-6.536	Likely Benign	0.089	Likely Benign	Likely Benign										0.357	Likely Benign	-1.20	Neutral	0.009	Benign	0.008	Benign	4.76	Benign	0.03	Affected	3.77	5	0.1366	0.3884		-1	-3	4.6	42.08
c.3380G>T	G1127V 2D AIThe SynGAP1 missense variant G1127V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443932‑G‑T). All available in silico predictors classify the change as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic prediction. Grouping by agreement, the benign‑predicting tools comprise the entire set, while no pathogenic predictions exist. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.852422	Binding	0.344	0.915	0.875					Uncertain		1	6-33443932-G-T	1	6.69e-7	-6.097	Likely Benign	0.094	Likely Benign	Likely Benign										0.230	Likely Benign	-1.01	Neutral	0.004	Benign	0.005	Benign	4.81	Benign	0.17	Tolerated	4.32	4	0.1281	0.3669		-1	-3	4.6	42.08
c.3383G>T	G1128V 2D AIThe SynGAP1 missense variant G1128V is reported in gnomAD (variant ID 6‑33443935‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is 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 the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.865136	Binding	0.309	0.911	0.875								6-33443935-G-T			-5.111	Likely Benign	0.081	Likely Benign	Likely Benign										0.399	Likely Benign	-0.69	Neutral	0.611	Possibly Damaging	0.185	Benign	4.39	Benign	0.09	Tolerated	4.32	4	0.1358	0.3922		-3	-1	4.6	42.08
c.338G>T	G113V 2D AIThe SynGAP1 missense variant G113V is not reported 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		0.784345	Disordered	0.639486	Binding	0.350	0.870	0.750											-3.752	Likely Benign	0.188	Likely Benign	Likely Benign										0.124	Likely Benign	-1.77	Neutral	0.838	Possibly Damaging	0.145	Benign	4.18	Benign	0.05	Affected			0.1316	0.4002		-1	-3	4.6	42.08
c.359G>T	G120V 2D AIThe SynGAP1 missense variant G120V 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 not contradicted by any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.659993	Binding	0.359	0.887	0.750											-4.571	Likely Benign	0.107	Likely Benign	Likely Benign										0.036	Likely Benign	-0.68	Neutral	0.000	Benign	0.000	Benign	4.28	Benign	0.19	Tolerated			0.1321	0.3883		-1	-3	4.6	42.08
c.3791G>T	G1264V 2D AIThe SynGAP1 missense variant G1264V 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 from 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. 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	Coiled-coil	0.429200	Structured	0.762385	Binding	0.897	0.579	0.000											-6.116	Likely Benign	0.488	Ambiguous	Likely Benign										0.136	Likely Benign	-2.33	Neutral	0.966	Probably Damaging	0.617	Possibly Damaging	2.74	Benign	0.15	Tolerated			0.0972	0.3891		-1	-3	4.6	42.08
c.3908G>T	G1303V 2D AIThe SynGAP1 missense variant G1303V is not reported 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 not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.886612	Binding	0.429	0.854	0.875											-3.513	Likely Benign	0.162	Likely Benign	Likely Benign										0.147	Likely Benign	-2.44	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.79	Benign	0.02	Affected			0.1511	0.3508		-1	-3	4.6	42.08
c.392G>T	G131V 2D AIThe SynGAP1 missense variant G131V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a tie and is therefore unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no result for this variant. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-6.248	Likely Benign	0.795	Likely Pathogenic	Ambiguous										0.199	Likely Benign	-4.25	Deleterious	0.983	Probably Damaging	0.559	Possibly Damaging	3.92	Benign	0.00	Affected			0.1168	0.4175		-1	-3	4.6	42.08
c.3950G>T	G1317V 2D AIThe SynGAP1 missense variant G1317V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.971158	Binding	0.385	0.879	0.750											-4.604	Likely Benign	0.286	Likely Benign	Likely Benign										0.050	Likely Benign	-2.99	Deleterious	0.004	Benign	0.004	Benign	4.05	Benign	0.00	Affected			0.1132	0.3635		-1	-3	4.6	42.08
c.4004G>T	G1335V 2D AIThe SynGAP1 missense variant G1335V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for G1335V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750											-4.982	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1124	0.4195		-1	-3	4.6	42.08
c.644G>T	G215V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining twelve tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the variant as pathogenic. premPS is uncertain and does not influence the consensus. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or 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 any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000											-12.960	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.69	Destabilizing	0.2	5.41	Destabilizing	4.55	Destabilizing	0.53	Ambiguous	0.884	Likely Pathogenic	-7.66	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.56	Benign	0.00	Affected			0.1087	0.4777		-1	-3	4.6	42.08
c.680G>T	G227V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G227V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining twelve tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The high‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.106997	Structured	0.329995	Uncertain	0.800	0.329	0.250											-9.329	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	3.57	Destabilizing	0.4	6.24	Destabilizing	4.91	Destabilizing	0.78	Ambiguous	0.839	Likely Pathogenic	-7.58	Deleterious	0.952	Possibly Damaging	0.521	Possibly Damaging	5.67	Benign	0.01	Affected			0.1130	0.4703		-1	-3	4.6	42.08
c.77G>T	G26V 2D AIThe SynGAP1 missense variant G26V is reported in gnomAD (variant ID 6‑33423486‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicted set includes REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic‑predicted set contains polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No Foldetta stability result is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect for G26V, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375								6-33423486-G-T	1	6.20e-7	-3.499	Likely Benign	0.165	Likely Benign	Likely Benign										0.197	Likely Benign	-2.34	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.89	Benign	0.00	Affected	4.32	1	0.1344	0.4333		-3	-1	4.6	42.08
c.908G>T	G303V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G303V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign) all indicate a tolerated change. Pathogenic signals arise only from SIFT and FoldX, while Rosetta and Foldetta are inconclusive. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields Likely Benign, and Foldetta remains uncertain. Overall, the preponderance 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	C2	0.450668	Structured	0.271087	Uncertain	0.630	0.254	0.250											-3.046	Likely Benign	0.198	Likely Benign	Likely Benign	3.06	Destabilizing	0.6	-0.72	Ambiguous	1.17	Ambiguous	0.14	Likely Benign	0.071	Likely Benign	-1.57	Neutral	0.011	Benign	0.017	Benign	3.96	Benign	0.01	Affected			0.1002	0.4577		-1	-3	4.6	42.08
c.926G>T	G309V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125											-13.595	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.55	Destabilizing	0.5	3.61	Destabilizing	4.08	Destabilizing	0.76	Ambiguous	0.531	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1256	0.3910		-1	-3	4.6	42.08
c.1034T>G	L345R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L345R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict pathogenicity: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic prediction. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-10.325	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	0.96	Ambiguous	0.1	1.66	Ambiguous	1.31	Ambiguous	1.28	Destabilizing	0.247	Likely Benign	-3.98	Deleterious	0.993	Probably Damaging	0.796	Possibly Damaging	1.81	Pathogenic	0.04	Affected			0.1140	0.0685		-3	-2	-8.3	43.03
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.1100T>G	L367R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L367R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Those that predict a pathogenic effect are SIFT, FATHMM, and Rosetta. Tools with uncertain or inconclusive results are FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a benign impact, with a minority of pathogenic predictions. The variant’s status is not contradicted by ClinVar, as it is not yet classified there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-6.527	Likely Benign	0.515	Ambiguous	Likely Benign	0.68	Ambiguous	0.4	6.63	Destabilizing	3.66	Destabilizing	0.70	Ambiguous	0.196	Likely Benign	-0.39	Neutral	0.146	Benign	0.057	Benign	1.66	Pathogenic	0.02	Affected			0.1608	0.1173		-3	-2	-8.3	43.03
c.1205T>G	L402R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402R is listed in ClinVar as Pathogenic (ClinVar ID 559657.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the overwhelming agreement among pathogenic predictions and the concordance with ClinVar, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000					Likely Pathogenic		1				-13.800	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.10	Destabilizing	0.2	3.82	Destabilizing	3.96	Destabilizing	2.24	Destabilizing	0.522	Likely Pathogenic	-4.69	Deleterious	0.967	Probably Damaging	0.459	Possibly Damaging	3.69	Benign	0.00	Affected	3.38	28	0.1467	0.1173		-3	-2	-8.3	43.03	259.5	-55.4	0.0	0.0	1.4	0.0	X		X				X	Potentially Pathogenic	The iso-butyl side chain of Leu402, located in an anti-parallel β sheet strand (res. Ala399-Ile411), packs with residues inside the hydrophobic core of the C2 domain (e.g., Ile268, Ala404, Leu266, Val400). In the variant simulations, the positively charged guanidinium group of the Arg402 side chain is not suitable for the hydrophobic niche. Consequently, the side chain moves outward from the hydrophobic C2 domain core and stacks with the phenol ring of Tyr363 or forms H-bonds with the carboxamide group of the Gln361 side chain in the β sheet strand (res. Thr359-Tyr364). This movement induces extensive negative effects on the C2 domain structure.
c.1247T>G	L416R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L416R missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans toward benign, while Foldetta remains uncertain. Overall, the majority of reliable predictors classify the variant as benign, 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	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.600	Likely Pathogenic	0.511	Ambiguous	Likely Benign	0.71	Ambiguous	0.0	0.97	Ambiguous	0.84	Ambiguous	0.84	Ambiguous	0.238	Likely Benign	-2.05	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.35	Benign	0.43	Tolerated			0.1445	0.0702		-3	-2	-8.3	43.03
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.1316T>G	L439R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L439R lies 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 are limited to FATHMM, while the remaining evaluated algorithms (SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic or likely pathogenic impact; FoldX is uncertain and is treated as unavailable. 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) also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-12.870	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.90	Ambiguous	0.5	2.62	Destabilizing	2.26	Destabilizing	1.40	Destabilizing	0.554	Likely Pathogenic	-5.25	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.22	Benign	0.01	Affected			0.1217	0.0488		-3	-2	-8.3	43.03
c.1352T>G	L451R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). All available in‑silico predictors classify the substitution as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: 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) reports a pathogenic effect. Based on the unanimous pathogenic predictions and the absence of benign calls, 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	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-16.162	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.32	Destabilizing	0.1	3.76	Destabilizing	3.54	Destabilizing	2.25	Destabilizing	0.726	Likely Pathogenic	-5.82	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.1130	0.0558		-3	-2	-8.3	43.03
c.1364T>G	L455R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L455R 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 only FATHMM; all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-16.347	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	6.36	Destabilizing	0.2	4.96	Destabilizing	5.66	Destabilizing	2.08	Destabilizing	0.648	Likely Pathogenic	-5.73	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.24	Benign	0.00	Affected			0.1126	0.0600		-3	-2	-8.3	43.03
c.1394T>G	L465R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No inconclusive or missing results are present. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-17.976	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.52	Destabilizing	0.7	4.44	Destabilizing	4.48	Destabilizing	2.41	Destabilizing	0.761	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.1597	0.0963		-3	-2	-8.3	43.03
c.1445T>G	L482R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while FoldX, Rosetta, and Foldetta return uncertain results. In a consensus framework, the SGM‑Consensus score is “Likely Pathogenic,” reflecting the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus is Likely Pathogenic, and Foldetta remains inconclusive. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-14.684	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.31	Ambiguous	1.03	Ambiguous	1.53	Destabilizing	0.878	Likely Pathogenic	-5.92	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.01	Affected			0.1255	0.0679		-3	-2	-8.3	43.03
c.1448T>G	I483R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000											-17.066	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	5.14	Destabilizing	0.4	4.09	Destabilizing	4.62	Destabilizing	1.97	Destabilizing	0.595	Likely Pathogenic	-6.50	Deleterious	0.997	Probably Damaging	0.991	Probably Damaging	3.14	Benign	0.00	Affected			0.1120	0.0870		-2	-3	-9.0	43.03
c.1466T>G	L489R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized 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 destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-15.365	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.32	Destabilizing	0.3	4.90	Destabilizing	4.61	Destabilizing	1.74	Destabilizing	0.949	Likely Pathogenic	-5.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.61	Pathogenic	0.00	Affected			0.1306	0.1145		-3	-2	-8.3	43.03
c.1481T>G	I494R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I494R is listed in ClinVar as Pathogenic (ClinVar ID 1685460.0) and is not reported in gnomAD. Prediction tools that assess functional impact all converge on a pathogenic outcome: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000					Likely Pathogenic		1				-15.758	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	6.71	Destabilizing	0.3	3.40	Destabilizing	5.06	Destabilizing	2.19	Destabilizing	0.911	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.957	Probably Damaging	-1.41	Pathogenic	0.00	Affected	3.37	35	0.1180	0.0870		-2	-3	-9.0	43.03	273.9	-59.8	0.0	0.0	0.0	0.1	X	X	X				X	Potentially Pathogenic	The sec-butyl side chain of Ile494, located in an α-helix (res. Leu489-Glu519), packs against hydrophobic residues (e.g., Phe484, Leu465, Trp572, Ala493, Met468) in an inter-helix space (res. Leu489-Glu519 and res. Ala461-Phe476). In the variant simulations, the bulkier and positively charged residue, Arg494, weakens the integrity of the opposing helix. Additionally, the bulkier Arg494 stacks with Phe484, causing the α-helices to move farther apart to accommodate it. This mutation could have substantial negative effects due to the fundamental role of hydrophobic packing, which is disrupted by Arg494 during protein folding.
c.1499T>G	L500R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as pathogenic include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign effect; the benign group is empty. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overwhelming agreement among pathogenic predictors and the lack of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000											-15.576	Likely Pathogenic	0.789	Likely Pathogenic	Ambiguous	2.23	Destabilizing	0.1	1.04	Ambiguous	1.64	Ambiguous	1.11	Destabilizing	0.794	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.02	Pathogenic	0.03	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.1517T>G	L506R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Thus, all available evidence indicates that the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-14.119	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	4.92	Destabilizing	0.6	5.85	Destabilizing	5.39	Destabilizing	1.77	Destabilizing	0.738	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1207	0.0488		-3	-2	-8.3	43.03
c.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.1628T>G	L543R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a pathogenic impact. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000											-18.563	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.47	Destabilizing	1.2	8.02	Destabilizing	5.75	Destabilizing	1.64	Destabilizing	0.739	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.89	Pathogenic	0.00	Affected			0.1229	0.0488		-3	-2	-8.3	43.03
c.1652T>G	L551R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551R 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 REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain outcome is FoldX. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the concordant predictions from multiple independent algorithms and the absence of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000											-15.420	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.81	Ambiguous	0.2	2.35	Destabilizing	2.08	Destabilizing	2.09	Destabilizing	0.949	Likely Pathogenic	-3.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.60	Pathogenic	0.01	Affected			0.1278	0.0530		-3	-2	-8.3	43.03
c.167T>G	L56R 2D AIThe SynGAP1 missense variant L56R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (5 pathogenic vs 3 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-10.194	Likely Pathogenic	0.918	Likely Pathogenic	Ambiguous										0.264	Likely Benign	-1.92	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.79	Benign	0.00	Affected			0.1191	0.0685		-3	-2	-8.3	43.03
c.1694T>G	L565R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565R is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33440746‑T‑G). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM Consensus—consistently predict a pathogenic impact. The Rosetta stability assessment is inconclusive and is therefore treated as unavailable. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar evidence (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000								6-33440746-T-G			-16.070	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.71	Destabilizing	0.1	1.88	Ambiguous	3.30	Destabilizing	2.66	Destabilizing	0.547	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.74	Benign	0.00	Affected	3.37	35	0.1373	0.0615		-2	-3	-8.3	43.03
c.170T>G	L57R 2D AIThe SynGAP1 missense variant L57R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-6.034	Likely Benign	0.810	Likely Pathogenic	Ambiguous										0.213	Likely Benign	-1.55	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.91	Benign	0.00	Affected			0.1245	0.0685		-3	-2	-8.3	43.03
c.1721T>G	L574R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L574R is not 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, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and FATHMM. Two tools remain inconclusive: Rosetta (Uncertain) and AlphaMissense‑Default (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors (seven benign vs. three pathogenic) support a benign classification, and this conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.083462	Structured	0.026427	Uncertain	0.927	0.246	0.000											-8.702	Likely Pathogenic	0.563	Ambiguous	Likely Benign	0.04	Likely Benign	0.2	0.88	Ambiguous	0.46	Likely Benign	-0.12	Likely Benign	0.322	Likely Benign	0.30	Neutral	0.907	Possibly Damaging	0.292	Benign	-1.22	Pathogenic	0.52	Tolerated			0.1419	0.0530		-3	-2	-8.3	43.03
c.1763T>G	L588R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods corroborate this: 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. All available evidence points to a deleterious impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-15.602	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	6.96	Destabilizing	0.4	6.14	Destabilizing	6.55	Destabilizing	2.07	Destabilizing	0.942	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.1209	0.0530		-3	-2	-8.3	43.03
c.176T>G	L59R 2D AISynGAP1 missense variant L59R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. The predictions are therefore split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools provide contradictory signals. Consequently, the variant is most likely pathogenic based on the presence of multiple pathogenic predictions and the high‑accuracy AlphaMissense‑Optimized result, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-4.037	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.266	Likely Benign	-2.09	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.26	Benign	0.00	Affected			0.1298	0.0600		-3	-2	-8.3	43.03
c.1778T>G	L593R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L593R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-16.139	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.27	Destabilizing	0.3	3.39	Destabilizing	3.83	Destabilizing	2.11	Destabilizing	0.740	Likely Pathogenic	-5.87	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.77	Benign	0.00	Affected			0.1440	0.0615		-3	-2	-8.3	43.03
c.1784T>G	L595R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, while the majority of tools (SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and Foldetta are uncertain. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Overall, the evidence strongly favors a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000											-14.601	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	1.22	Ambiguous	0.0	2.20	Destabilizing	1.71	Ambiguous	1.52	Destabilizing	0.707	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.76	Benign	0.00	Affected			0.1344	0.1005		-3	-2	-8.3	43.03
c.1793T>G	L598R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among 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	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-17.392	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.70	Destabilizing	0.5	3.06	Destabilizing	2.88	Destabilizing	2.23	Destabilizing	0.682	Likely Pathogenic	-5.87	Deleterious	0.999	Probably Damaging	0.973	Probably Damaging	3.10	Benign	0.00	Affected			0.1297	0.0679		-3	-2	-8.3	43.03
c.1820T>G	L607R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. All other evaluated algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. Rosetta and Foldetta provide uncertain results and are therefore treated as unavailable evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” while Foldetta remains uncertain. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-14.234	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	-0.15	Likely Benign	0.1	1.48	Ambiguous	0.67	Ambiguous	1.24	Destabilizing	0.920	Likely Pathogenic	-5.98	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.51	Pathogenic	0.01	Affected			0.1490	0.0615		-3	-2	-8.3	43.03
c.1829T>G	L610R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic outcome; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-13.855	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	5.14	Destabilizing	0.5	4.60	Destabilizing	4.87	Destabilizing	1.89	Destabilizing	0.949	Likely Pathogenic	-5.94	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.58	Pathogenic	0.00	Affected			0.1334	0.0615		-3	-2	-8.3	43.03
c.1868T>G	L623R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623R is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-13.718	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.08	Destabilizing	1.4	3.28	Destabilizing	3.68	Destabilizing	2.31	Destabilizing	0.795	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1327	0.0615		-3	-2	-8.3	43.03
c.1874T>G	L625R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L625R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-14.507	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	2.31	Destabilizing	0.7	4.21	Destabilizing	3.26	Destabilizing	1.88	Destabilizing	0.733	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.99	Benign	0.00	Affected			0.1091	0.0615		-3	-2	-8.3	43.03
c.1898T>G	L633R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts 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. Based on the overwhelming consensus of pathogenic predictions and the absence of any benign signal, 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	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000											-14.360	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.41	Destabilizing	0.2	4.85	Destabilizing	4.63	Destabilizing	2.15	Destabilizing	0.667	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.00	Affected			0.1674	0.0518		-3	-2	-8.3	43.03
c.191T>G	I64R 2D AIThe SynGAP1 missense variant I64R is not reported in ClinVar and has no entry in gnomAD. 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 score 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 absence of a ClinVar assertion, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.475481	Uncertain	0.478	0.747	0.125											-2.108	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-0.54	Neutral	0.842	Possibly Damaging	0.068	Benign	4.05	Benign	0.00	Affected			0.1103	0.0940		-2	-3	-9.0	43.03
c.1937T>G	L646R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact. Overall, the preponderance of evidence points to a pathogenic effect for L646R, 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	0.303751	Uncertain	0.941	0.344	0.000											-12.393	Likely Pathogenic	0.920	Likely Pathogenic	Ambiguous	4.44	Destabilizing	0.2	3.94	Destabilizing	4.19	Destabilizing	2.75	Destabilizing	0.455	Likely Benign	-3.56	Deleterious	0.014	Benign	0.002	Benign	3.17	Benign	0.03	Affected			0.2304	0.1405		-3	-2	-8.3	43.03
c.1958T>G	L653R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L653R lies 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 are limited to FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.335213	Uncertain	0.963	0.332	0.000											-16.078	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	6.92	Destabilizing	1.1	5.84	Destabilizing	6.38	Destabilizing	2.55	Destabilizing	0.649	Likely Pathogenic	-5.75	Deleterious	0.997	Probably Damaging	0.806	Possibly Damaging	3.09	Benign	0.00	Affected			0.1501	0.0805		-3	-2	-8.3	43.03
c.1964T>G	L655R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, and the majority of consensus methods (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all score the variant as benign. The only inconclusive result comes from Rosetta, which is treated as unavailable. High‑accuracy assessments reinforce this benign prediction: 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 predicts benign. Thus, based on the available predictions, 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	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-4.848	Likely Benign	0.284	Likely Benign	Likely Benign	-0.40	Likely Benign	0.0	0.54	Ambiguous	0.07	Likely Benign	-0.09	Likely Benign	0.160	Likely Benign	0.46	Neutral	0.006	Benign	0.001	Benign	3.50	Benign	0.60	Tolerated			0.1589	0.0615		-3	-2	-8.3	43.03
c.2009T>G	L670R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign effect. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.801	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	1.42	Ambiguous	1.03	Ambiguous	0.67	Ambiguous	0.193	Likely Benign	-1.74	Neutral	0.993	Probably Damaging	0.755	Possibly Damaging	3.43	Benign	0.41	Tolerated			0.1327	0.1145		-3	-2	-8.3	43.03
c.200T>G	L67R 2D AIThe SynGAP1 missense variant L67R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Thus, the variant is most likely benign based on current predictive tools. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-3.430	Likely Benign	0.814	Likely Pathogenic	Ambiguous										0.115	Likely Benign	-0.84	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.09	Benign	0.00	Affected			0.1159	0.0719		-3	-2	-8.3	43.03
c.2018T>G	L673R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L673R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). FoldX and Foldetta are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and an uncertain outcome from Foldetta. Overall, the majority of evidence points toward pathogenicity, and this conclusion does not conflict with 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	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-14.474	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	2.04	Destabilizing	1.57	Ambiguous	1.23	Destabilizing	0.178	Likely Benign	-3.81	Deleterious	0.991	Probably Damaging	0.433	Benign	3.36	Benign	0.03	Affected			0.1348	0.1015		-3	-2	-8.3	43.03
c.203T>G	L68R 2D AIThe SynGAP1 missense variant L68R is not reported 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 impact. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic effect. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar 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		0.534167	Disordered	0.470567	Uncertain	0.405	0.768	0.250											-3.427	Likely Benign	0.865	Likely Pathogenic	Ambiguous										0.147	Likely Benign	-0.61	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.13	Benign	0.00	Affected			0.1178	0.0519		-3	-2	-8.3	43.03
c.2066T>G	L689R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-17.776	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.91	Destabilizing	0.6	5.61	Destabilizing	5.76	Destabilizing	2.14	Destabilizing	0.609	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.932	Probably Damaging	3.15	Benign	0.00	Affected			0.1208	0.0530		-3	-2	-8.3	43.03
c.2075T>G	L692R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692R is 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	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-16.656	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.34	Destabilizing	0.0	5.51	Destabilizing	4.93	Destabilizing	1.96	Destabilizing	0.611	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.07	Benign	0.00	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.2084T>G	L695R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the variant as pathogenic. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. Overall, the evidence overwhelmingly 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	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-15.582	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.1	2.66	Destabilizing	2.36	Destabilizing	1.57	Destabilizing	0.605	Likely Pathogenic	-5.92	Deleterious	0.993	Probably Damaging	0.588	Possibly Damaging	3.17	Benign	0.00	Affected			0.1220	0.0530		-3	-2	-8.3	43.03
c.2087T>G	L696R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L696R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: all available predictors except FATHMM (which flags it as benign) report pathogenicity. The benign group contains only FATHMM; the pathogenic group includes SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: 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 predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-19.609	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.67	Destabilizing	0.0	5.36	Destabilizing	4.52	Destabilizing	2.44	Destabilizing	0.624	Likely Pathogenic	-5.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.01	Benign	0.00	Affected			0.1200	0.0688		-3	-2	-8.3	43.03
c.2099T>G	L700R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L700R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, SGM Consensus remains Likely Pathogenic, and Foldetta predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-12.389	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.82	Ambiguous	0.1	4.19	Destabilizing	3.01	Destabilizing	1.89	Destabilizing	0.485	Likely Benign	-4.29	Deleterious	0.728	Possibly Damaging	0.249	Benign	3.35	Benign	0.01	Affected			0.1210	0.0488		-3	-2	-8.3	43.03
c.2108T>G	L703R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) all classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. The preponderance of pathogenic predictions, together with the high‑accuracy tools’ positive results, suggests that L703R is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.244	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	2.85	Destabilizing	0.0	3.74	Destabilizing	3.30	Destabilizing	1.79	Destabilizing	0.459	Likely Benign	-4.92	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.13	Benign	0.00	Affected			0.1223	0.0488		-3	-2	-8.3	43.03
c.2123T>G	L708R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as Likely Pathogenic. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of tools (six pathogenic vs. four benign) and the SGM Consensus support a pathogenic classification, whereas AlphaMissense‑Optimized suggests benign. The variant is most likely pathogenic based on the collective predictions, 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	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-9.154	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.0	0.90	Ambiguous	0.89	Ambiguous	1.24	Destabilizing	0.249	Likely Benign	-4.18	Deleterious	0.988	Probably Damaging	0.598	Possibly Damaging	3.27	Benign	0.19	Tolerated			0.1091	0.0488		-3	-2	-8.3	43.03
c.2126T>G	L709R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709R is not 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, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. Tools with uncertain or inconclusive results are Rosetta, premPS, 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, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Overall, the majority of evidence indicates a benign impact for the variant, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-8.636	Likely Pathogenic	0.482	Ambiguous	Likely Benign	0.22	Likely Benign	0.0	0.68	Ambiguous	0.45	Likely Benign	0.62	Ambiguous	0.061	Likely Benign	-1.56	Neutral	0.906	Possibly Damaging	0.314	Benign	3.50	Benign	0.44	Tolerated			0.1127	0.0488		-3	-2	-8.3	43.03
c.2132T>G	L711R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711R lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming majority of computational evidence, the variant is most likely pathogenic, and this 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	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-14.009	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.71	Destabilizing	0.0	3.98	Destabilizing	3.85	Destabilizing	2.13	Destabilizing	0.432	Likely Benign	-5.71	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.35	Benign	0.00	Affected			0.1345	0.0488		-3	-2	-8.3	43.03
c.2141T>G	L714R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L714R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-12.763	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.38	Destabilizing	0.2	7.54	Destabilizing	5.96	Destabilizing	2.09	Destabilizing	0.402	Likely Benign	-5.62	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.09	Benign	0.00	Affected			0.1186	0.0558		-3	-2	-8.3	43.03
c.2150T>G	L717R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717R is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the majority‑vote SGM Consensus) predict pathogenicity; FoldX is uncertain. High‑accuracy methods reinforce a pathogenic verdict: AlphaMissense‑Optimized scores it as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. No prediction is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.352	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	3.78	Destabilizing	2.72	Destabilizing	1.57	Destabilizing	0.353	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.28	Benign	0.00	Affected			0.1169	0.0558		-3	-2	-8.3	43.03
c.2153T>G	L718R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-16.119	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.90	Destabilizing	0.2	5.05	Destabilizing	5.48	Destabilizing	2.57	Destabilizing	0.484	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1254	0.0600		-3	-2	-8.3	43.03
c.2174T>G	L725R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. FoldX and Foldetta report uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta remains uncertain. Based on the overwhelming majority of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.383	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.3	2.16	Destabilizing	1.43	Ambiguous	1.49	Destabilizing	0.345	Likely Benign	-5.46	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1374	0.0846		-3	-2	-8.3	43.03
c.2243T>G	L748R 2D AIThe SynGAP1 missense variant L748R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441708‑T‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750					Conflicting		2	6-33441708-T-G	3	1.86e-6	-3.331	Likely Benign	0.245	Likely Benign	Likely Benign										0.055	Likely Benign	-0.67	Neutral	0.912	Possibly Damaging	0.448	Possibly Damaging	2.73	Benign	0.02	Affected	4.32	2	0.1342	0.0888		-3	-2	-8.3	43.03
c.2288T>G	L763R 2D AIThe SynGAP1 missense variant L763R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-5.516	Likely Benign	0.643	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-1.66	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.38	Pathogenic	0.07	Tolerated			0.1199	0.0761		-3	-2	-8.3	43.03
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.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.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.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.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.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.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.2504T>G	L835R 2D AIThe SynGAP1 missense variant L835R is not reported 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. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign 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		0.608892	Disordered	0.642742	Binding	0.319	0.863	0.125											-4.749	Likely Benign	0.381	Ambiguous	Likely Benign										0.126	Likely Benign	-1.05	Neutral	0.996	Probably Damaging	0.955	Probably Damaging	2.70	Benign	0.02	Affected			0.1239	0.0804		-3	-2	-8.3	43.03
c.2531T>G	L844R 2D AIThe SynGAP1 missense variant L844R is not 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, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that 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		0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											-9.355	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous										0.267	Likely Benign	-2.77	Deleterious	0.960	Probably Damaging	0.697	Possibly Damaging	2.60	Benign	0.01	Affected			0.1230	0.0947		-3	-2	-8.3	43.03
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.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.2606T>G	L869R 2D AIThe SynGAP1 missense variant L869R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this conclusion, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.688653	Binding	0.272	0.839	0.250											-2.546	Likely Benign	0.567	Likely Pathogenic	Likely Benign										0.170	Likely Benign	-0.79	Neutral	0.970	Probably Damaging	0.801	Possibly Damaging	2.60	Benign	0.29	Tolerated			0.1162	0.0846		-3	-2	-8.3	43.03
c.2609T>G	L870R 2D AIThe SynGAP1 missense variant L870R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L870R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.578	Likely Benign	0.636	Likely Pathogenic	Likely Benign										0.175	Likely Benign	-1.97	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.02	Affected			0.1147	0.0846		-3	-2	-8.3	43.03
c.2630T>G	L877R 2D AIThe SynGAP1 missense variant L877R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion 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.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-6.678	Likely Benign	0.673	Likely Pathogenic	Likely Benign										0.148	Likely Benign	-1.82	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.57	Benign	0.02	Affected			0.1218	0.0761		-3	-2	-8.3	43.03
c.2648T>G	L883R 2D AIThe SynGAP1 missense variant L883R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments 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 points to a benign impact for the L883R 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		0.716283	Disordered	0.641952	Binding	0.334	0.886	0.250											-3.026	Likely Benign	0.286	Likely Benign	Likely Benign										0.110	Likely Benign	-0.83	Neutral	0.934	Possibly Damaging	0.435	Benign	2.73	Benign	0.11	Tolerated			0.1237	0.1147		-3	-2	-8.3	43.03
c.2672T>G	L891R 2D AIThe SynGAP1 missense variant L891R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and the protein‑folding stability tool Foldetta has no available result for this variant. Based on the aggregate 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		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-4.120	Likely Benign	0.419	Ambiguous	Likely Benign										0.122	Likely Benign	-1.83	Neutral	0.970	Probably Damaging	0.801	Possibly Damaging	2.65	Benign	0.01	Affected			0.1233	0.0863		-3	-2	-8.3	43.03
c.2717T>G	L906R 2D AIThe SynGAP1 missense variant L906R is not 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 SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors (5 vs 4) lean toward pathogenicity, while the high‑accuracy AlphaMissense‑Optimized predicts benign and the consensus remains unresolved. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-3.440	Likely Benign	0.769	Likely Pathogenic	Likely Benign										0.160	Likely Benign	-0.26	Neutral	1.000	Probably Damaging	0.990	Probably Damaging	2.18	Pathogenic	0.04	Affected			0.1228	0.0947		-3	-2	-8.3	43.03
c.2762T>G	L921R 2D AIThe SynGAP1 missense variant L921R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375											-2.205	Likely Benign	0.563	Ambiguous	Likely Benign										0.217	Likely Benign	-1.19	Neutral	0.994	Probably Damaging	0.912	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1306	0.0761		-3	-2	-8.3	43.03
c.2774T>G	L925R 2D AIThe SynGAP1 missense variant L925R is 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 ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus indicates a likely pathogenic classification. Foldetta results are not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-2.340	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic										0.519	Likely Pathogenic	-4.54	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1278	0.1294		-3	-2	-8.3	43.03
c.2792T>G	L931R 2D AIThe SynGAP1 missense variant L931R is 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-8.606	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous										0.344	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.39	Pathogenic	0.01	Affected			0.1241	0.1205		-3	-2	-8.3	43.03
c.2963T>G	L988R 2D AIThe SynGAP1 missense variant L988R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-4.412	Likely Benign	0.681	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-2.39	Neutral	0.954	Possibly Damaging	0.867	Possibly Damaging	2.69	Benign	0.00	Affected			0.1257	0.1088		-3	-2	-8.3	43.03
c.3002T>G	L1001R 2D AIThe SynGAP1 missense variant L1001R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375											-2.285	Likely Benign	0.320	Likely Benign	Likely Benign										0.091	Likely Benign	-1.09	Neutral	0.966	Probably Damaging	0.708	Possibly Damaging	2.67	Benign	0.00	Affected			0.1299	0.0832		-3	-2	-8.3	43.03
c.3065T>G	L1022R 2D AIThe SynGAP1 missense variant L1022R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L1022R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-2.875	Likely Benign	0.659	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.96	Neutral	0.986	Probably Damaging	0.894	Possibly Damaging	2.51	Benign	0.01	Affected			0.1279	0.1387		-3	-2	-8.3	43.03
c.3071T>G	L1024R 2D AIThe SynGAP1 missense variant L1024R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic interpretation. This assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-3.434	Likely Benign	0.841	Likely Pathogenic	Ambiguous										0.148	Likely Benign	-2.41	Neutral	0.997	Probably Damaging	0.962	Probably Damaging	2.40	Pathogenic	0.02	Affected			0.1335	0.1557		-3	-2	-8.3	43.03
c.3083T>G	L1028R 2D AIThe SynGAP1 missense variant L1028R is not reported 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 (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-2.204	Likely Benign	0.793	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-0.24	Neutral	0.960	Probably Damaging	0.761	Possibly Damaging	2.75	Benign	0.84	Tolerated			0.1328	0.1603		-3	-2	-8.3	43.03
c.3095T>G	L1032R 2D AIThe SynGAP1 missense variant L1032R is not reported 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995318	Binding	0.365	0.735	0.500											-2.658	Likely Benign	0.707	Likely Pathogenic	Likely Benign										0.099	Likely Benign	-1.03	Neutral	0.995	Probably Damaging	0.892	Possibly Damaging	2.66	Benign	0.02	Affected			0.1350	0.1919		-3	-2	-8.3	43.03
c.3272T>G	L1091R 2D AIThe SynGAP1 missense variant L1091R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) suggest a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000											-3.662	Likely Benign	0.896	Likely Pathogenic	Ambiguous										0.191	Likely Benign	-1.51	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.47	Pathogenic	0.02	Affected			0.1274	0.1357		-3	-2	-8.3	43.03
c.3326T>G	L1109R 2D AIThe SynGAP1 missense variant L1109R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The 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 is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this 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		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875											-5.440	Likely Benign	0.408	Ambiguous	Likely Benign										0.139	Likely Benign	-0.70	Neutral	0.586	Possibly Damaging	0.225	Benign	2.68	Benign	0.34	Tolerated			0.1352	0.1919		-3	-2	-8.3	43.03
c.3386T>G	L1129R 2D AIThe SynGAP1 missense variant L1129R is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates 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		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875											-2.613	Likely Benign	0.442	Ambiguous	Likely Benign										0.376	Likely Benign	-1.68	Neutral	0.005	Benign	0.007	Benign	5.48	Benign	0.00	Affected			0.1334	0.1636		-3	-2	-8.3	43.03
c.3491T>G	L1164R 2D AIThe SynGAP1 missense variant L1164R has no ClinVar entry and is absent from gnomAD, so its population frequency is unknown. Functional prediction tools show mixed results: benign calls come from PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and AlphaMissense‑Optimized. Grouping by consensus, four tools predict benign and five predict pathogenic. High‑accuracy methods give a more nuanced view: the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign outcome; AlphaMissense‑Optimized independently predicts Pathogenic; Foldetta’s stability assessment is unavailable. Overall, the majority of standard predictors lean toward pathogenicity, but the SGM Consensus and several benign‑oriented tools counterbalance this. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of predictions, though the SGM Consensus suggests a benign interpretation, indicating uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.853935	Binding	0.325	0.815	0.375											-4.390	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.539	Likely Pathogenic	-1.65	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.33	Benign	0.08	Tolerated			0.1396	0.0623		-3	-2	-8.3	43.03
c.3539T>G	L1180R 2D AIThe SynGAP1 missense variant L1180R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available. Overall, the majority of evidence—including the SGM Consensus and several benign‑predicting tools—suggests 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.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.238	Likely Benign	0.920	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-1.58	Neutral	0.977	Probably Damaging	0.900	Possibly Damaging	2.67	Benign	0.00	Affected			0.1199	0.0660		-3	-2	-8.3	43.03
c.3575T>G	L1192R 2D AIThe SynGAP1 missense variant L1192R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-3.221	Likely Benign	0.695	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.33	Neutral	0.992	Probably Damaging	0.940	Probably Damaging	2.75	Benign	0.35	Tolerated			0.1148	0.0558		-3	-2	-8.3	43.03
c.3614T>G	L1205R 2D AIThe SynGAP1 missense variant L1205R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-16.706	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.451	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1081	0.0558		-3	-2	-8.3	43.03
c.3626T>G	L1209R 2D AIThe SynGAP1 missense variant L1209R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its influence is unavailable. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that the variant is most likely pathogenic, with no conflict from ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-17.481	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.438	Likely Benign	-5.12	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1129	0.0558		-3	-2	-8.3	43.03
c.3647T>G	L1216R 2D AIThe SynGAP1 missense variant L1216R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-9.700	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.387	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.16	Pathogenic	0.00	Affected			0.1071	0.0488		-3	-2	-8.3	43.03
c.3668T>G	L1223R 2D AIThe SynGAP1 missense variant L1223R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of computational evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-15.396	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1078	0.0919		-3	-2	-8.3	43.03
c.3671T>G	L1224R 2D AIThe SynGAP1 missense variant L1224R is listed in ClinVar with no assertion (ClinVar status: None) and is present in the gnomAD database (ID 6‑33446663‑T‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500								6-33446663-T-G	1	6.20e-7	-7.504	In-Between	0.220	Likely Benign	Likely Benign										0.113	Likely Benign	-1.85	Neutral	0.989	Probably Damaging	0.900	Possibly Damaging	2.42	Pathogenic	0.33	Tolerated	3.77	5	0.1120	0.0558		-2	-3	-8.3	43.03
c.3701T>G	L1234R 2D AIThe SynGAP1 missense change L1234R occurs in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-15.015	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.211	Likely Benign	-4.52	Deleterious	0.997	Probably Damaging	0.939	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1061	0.0849		-3	-2	-8.3	43.03
c.3722T>G	L1241R 2D AIThe SynGAP1 missense variant L1241R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, 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 is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-14.178	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.3743T>G	L1248R 2D AIThe SynGAP1 missense variant L1248R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-11.285	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.1222	0.0488		-3	-2	-8.3	43.03
c.3797T>G	L1266R 2D AISynGAP1 missense variant L1266R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta results are unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools points to a pathogenic effect, with no conflict from ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-16.676	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.391	Likely Benign	-5.04	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1063	0.0891		-3	-2	-8.3	43.03
c.3803T>G	L1268R 2D AIThe SynGAP1 missense change L1268R is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign) all support a neutral impact. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy tools reinforce the benign assessment: AlphaMissense‑Optimized returns a benign prediction and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are not available, so they do not influence the interpretation. Overall, the preponderance of evidence points to a benign effect for L1268R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000											-7.010	In-Between	0.293	Likely Benign	Likely Benign										0.076	Likely Benign	-0.79	Neutral	0.970	Probably Damaging	0.637	Possibly Damaging	2.68	Benign	0.08	Tolerated			0.1135	0.0558		-3	-2	-8.3	43.03
c.3818T>G	L1273R 2D AIThe SynGAP1 missense variant L1273R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment is not contradicted by any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.252	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.431	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.934	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1369	0.0761		-3	-2	-8.3	43.03
c.3851T>G	L1284R 2D AIThe SynGAP1 missense variant L1284R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. This assessment 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.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875											-4.203	Likely Benign	0.156	Likely Benign	Likely Benign										0.163	Likely Benign	-3.11	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.00	Affected			0.1216	0.0488		-3	-2	-8.3	43.03
c.3872T>G	L1291R 2D AIThe SynGAP1 missense variant L1291R is not reported in ClinVar and is present in gnomAD (ID 6‑33447920‑T‑G). 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. High‑accuracy assessment shows AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and Foldetta results are unavailable. Overall, the majority of conventional predictors indicate a pathogenic effect, whereas the single high‑accuracy tool suggests benign. No ClinVar annotation contradicts these findings. Thus, based on the collective evidence, the variant is most likely pathogenic, though the high‑accuracy prediction introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625								6-33447920-T-G	1	6.44e-7	-3.977	Likely Benign	0.302	Likely Benign	Likely Benign										0.287	Likely Benign	-4.29	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	2.49	Pathogenic	0.00	Affected	3.77	5	0.1160	0.1049		-2	-3	-8.3	43.03
c.3875T>G	L1292R 2D AIThe SynGAP1 missense variant L1292R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward a pathogenic interpretation. This prediction does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625											-4.249	Likely Benign	0.238	Likely Benign	Likely Benign										0.223	Likely Benign	-4.34	Deleterious	0.971	Probably Damaging	0.773	Possibly Damaging	2.46	Pathogenic	0.00	Affected			0.1286	0.0849		-3	-2	-8.3	43.03
c.3896T>G	L1299R 2D AIThe SynGAP1 missense variant L1299R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for 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		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-3.080	Likely Benign	0.260	Likely Benign	Likely Benign										0.293	Likely Benign	-3.75	Deleterious	0.971	Probably Damaging	0.597	Possibly Damaging	2.68	Benign	0.01	Affected			0.1366	0.1147		-3	-2	-8.3	43.03
c.3932T>G	L1311R 2D AIThe SynGAP1 missense variant L1311R is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the change as tolerated or benign. Only polyPhen‑2 HumDiv classifies 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 classification. High‑accuracy tools further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the evidence overwhelmingly 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		0.816150	Disordered	0.968153	Binding	0.393	0.907	0.750											-3.794	Likely Benign	0.169	Likely Benign	Likely Benign										0.083	Likely Benign	-0.36	Neutral	0.579	Possibly Damaging	0.267	Benign	2.74	Benign	0.12	Tolerated			0.1611	0.1719		-3	-2	-8.3	43.03
c.3953T>G	L1318R 2D AIThe SynGAP1 missense variant L1318R is reported in gnomAD (variant ID 6-33451827‑T‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (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 both general and high‑accuracy predictors points to a benign effect, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.968271	Binding	0.399	0.865	0.750								6-33451827-T-G			-3.381	Likely Benign	0.187	Likely Benign	Likely Benign										0.081	Likely Benign	-1.58	Neutral	0.588	Possibly Damaging	0.212	Benign	4.01	Benign	0.01	Affected	3.77	5	0.1429	0.1303		-2	-3	-8.3	43.03
c.3986T>G	L1329R 2D AIThe SynGAP1 missense variant L1329R is catalogued in gnomAD (ID 6‑33451860‑T‑G) but has no ClinVar submission. Functional prediction tools cluster into two groups: benign predictions from REVEL, ESM1b, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑to‑2 split. No Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors (five pathogenic vs three benign) lean toward a pathogenic effect. Because ClinVar contains no classification, there is no conflict with existing clinical annotations. Thus, based on current in silico evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-G			-3.636	Likely Benign	0.923	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-3.16	Deleterious	0.994	Probably Damaging	0.990	Probably Damaging	3.05	Benign	0.00	Affected	3.77	5	0.1594	0.1547		-2	-3	-8.3	43.03
c.398T>G	L133R 2D AIThe SynGAP1 missense variant L133R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome (3 pathogenic vs. 1 benign votes). AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a pathogenic classification for L133R, and this assessment does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-8.857	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.389	Likely Benign	-2.57	Deleterious	0.002	Benign	0.005	Benign	3.55	Benign	0.00	Affected			0.1522	0.0479		-3	-2	-8.3	43.03
c.410T>G	L137R 2D AIThe SynGAP1 missense variant L137R is not 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. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support 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. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-11.595	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.334	Likely Benign	-3.50	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.60	Benign	0.00	Affected			0.1300	0.0691		-3	-2	-8.3	43.03
c.449T>G	L150R 2D AIThe SynGAP1 missense variant L150R is not 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, and PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools points to a pathogenic effect for the SynGAP1 L150R variant, 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		0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-14.879	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.16	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.67	Benign	0.00	Affected			0.1275	0.0719		-3	-2	-8.3	43.03
c.479T>G	L160R 2D AIThe SynGAP1 missense variant L160R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The protein‑folding stability method Foldetta did not provide a result, so its status is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-14.539	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.83	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.90	Benign	0.00	Affected			0.1482	0.0702		-3	-2	-8.3	43.03
c.518T>G	L173R 2D AIThe SynGAP1 missense variant L173R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, 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 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools lean toward a benign interpretation, and there is no ClinVar evidence to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-9.524	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous										0.119	Likely Benign	-1.63	Neutral	0.561	Possibly Damaging	0.178	Benign	3.95	Benign	0.08	Tolerated			0.1258	0.0761		-3	-2	-8.3	43.03
c.560T>G	L187R 2D AIThe SynGAP1 missense variant L187R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a deleterious effect, and the SGM‑Consensus (derived from 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 both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-14.118	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.332	Likely Benign	-4.38	Deleterious	0.917	Possibly Damaging	0.467	Possibly Damaging	3.72	Benign	0.00	Affected			0.1481	0.0702		-3	-2	-8.3	43.03
c.593T>G	L198R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198R is not 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 a 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). Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-15.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.2	1.56	Ambiguous	1.15	Ambiguous	0.69	Ambiguous	0.410	Likely Benign	-4.98	Deleterious	0.982	Probably Damaging	0.648	Possibly Damaging	3.34	Benign	0.00	Affected			0.1180	0.0719		-3	-2	-8.3	43.03
c.641T>G	L214R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L214R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are 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 uncertain. Overall, the evidence strongly favors a pathogenic effect for this variant, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-11.458	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.35	Ambiguous	0.6	0.92	Ambiguous	1.14	Ambiguous	1.68	Destabilizing	0.927	Likely Pathogenic	-4.98	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	5.75	Benign	0.00	Affected			0.1335	0.0772		-3	-2	-8.3	43.03
c.737T>G	L246R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L246R missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—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 reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.472492	Structured	0.302312	Uncertain	0.859	0.364	0.000											-13.849	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.94	Destabilizing	0.8	2.77	Destabilizing	3.36	Destabilizing	1.72	Destabilizing	0.925	Likely Pathogenic	-5.43	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	4.67	Benign	0.00	Affected			0.1266	0.0600		-3	-2	-8.3	43.03
c.791T>G	L264R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L264R 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. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000											-16.976	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.25	Destabilizing	0.3	3.37	Destabilizing	3.81	Destabilizing	2.28	Destabilizing	0.742	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.49	Pathogenic	0.00	Affected			0.1132	0.0558		-3	-2	-8.3	43.03
c.797T>G	L266R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L266R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy assessments reinforce this view: 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. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.232838	Structured	0.297157	Uncertain	0.948	0.264	0.000											-17.131	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.2	2.76	Destabilizing	3.37	Destabilizing	2.04	Destabilizing	0.574	Likely Pathogenic	-5.32	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.1059	0.0558		-3	-2	-8.3	43.03
c.806T>G	I269R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I269R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, whereas the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta give uncertain results, and Foldetta is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.343787	Uncertain	0.937	0.244	0.125											-14.567	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.1	1.99	Ambiguous	1.67	Ambiguous	1.50	Destabilizing	0.765	Likely Pathogenic	-5.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.07	Tolerated			0.1108	0.0870		-2	-3	-9.0	43.03
c.821T>G	L274R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L274R is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all agree on 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 predict a pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available predictions and stability analyses are concordant and indicate a likely pathogenic impact. Thus, based on the current computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.066181	Structured	0.377483	Uncertain	0.866	0.195	0.250											-17.691	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.61	Destabilizing	0.8	3.15	Destabilizing	3.38	Destabilizing	1.56	Destabilizing	0.807	Likely Pathogenic	-5.45	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.00	Pathogenic	0.00	Affected			0.1404	0.0488		-3	-2	-8.3	43.03
c.851T>G	L284R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L284R is not reported in ClinVar and is absent from gnomAD. 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. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. With all available evidence pointing to a damaging effect and no ClinVar entry 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	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-17.698	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.05	Destabilizing	0.5	4.29	Destabilizing	4.67	Destabilizing	2.14	Destabilizing	0.797	Likely Pathogenic	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.1175	0.0600		-3	-2	-8.3	43.03
c.857T>G	L286R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L286R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while Rosetta remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (majority vote) is likely pathogenic; and Foldetta, which integrates FoldX‑MD (pathogenic) and Rosetta (uncertain), reports a pathogenic effect. 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	0.122885	Structured	0.385647	Uncertain	0.932	0.260	0.000											-15.563	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.3	1.80	Ambiguous	2.35	Destabilizing	1.97	Destabilizing	0.868	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.49	Pathogenic	0.00	Affected			0.1370	0.0600		-3	-2	-8.3	43.03
c.869T>G	L290R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L290R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions are limited to FoldX, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. Overall, the consensus of the majority of evidence points to a pathogenic impact. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.399723	Uncertain	0.904	0.255	0.000											-13.938	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.48	Likely Benign	0.1	0.88	Ambiguous	0.68	Ambiguous	0.89	Ambiguous	0.705	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.01	Affected			0.1215	0.1056		-3	-2	-8.3	43.03
c.950T>G	L317R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L317R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.106997	Structured	0.394031	Uncertain	0.874	0.240	0.125											-14.185	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.2	2.01	Destabilizing	2.67	Destabilizing	1.63	Destabilizing	0.569	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.1501	0.0893		-3	-2	-8.3	43.03
c.968T>G	L323R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L323R is listed in ClinVar (ID 978601.0) as Pathogenic and is not reported in gnomAD. All available in‑silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Consequently, 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	0.268042	Structured	0.428564	Uncertain	0.956	0.369	0.000					Likely Pathogenic		1				-14.568	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.75	Destabilizing	0.4	4.47	Destabilizing	4.11	Destabilizing	2.15	Destabilizing	0.692	Likely Pathogenic	-4.70	Deleterious	0.999	Probably Damaging	0.969	Probably Damaging	0.59	Pathogenic	0.01	Affected	3.39	22	0.1066	0.0600		-3	-2	-8.3	43.03	261.8	-61.6	-0.4	0.2	0.8	0.2	X		X				X	Potentially Pathogenic	The iso-butyl side chain of Leu323, located at the beginning of an anti-parallel β sheet strand (res. Ala322-Asp330), packs against multiple hydrophobic leucine residues (e.g., Leu264, Leu266, Leu284, Leu286). In contrast, in the variant simulations, the positively charged guanidinium group of the Arg323 side chain is unsuitable for the hydrophobic niche. Consequently, the side chain either rotates away from the center of the C2 domain or, if it remains within the C2 domain core, it reorients nearby residues to form hydrogen bonds. Regardless, the residue swap extensively disrupts the C2 domain structure.
c.974T>G	L325R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L325R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on 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 predict a pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. No predictions or stability results are missing or inconclusive. **Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (no ClinVar entry).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.424577	Uncertain	0.955	0.436	0.000											-16.612	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.34	Destabilizing	0.3	4.11	Destabilizing	4.23	Destabilizing	1.94	Destabilizing	0.551	Likely Pathogenic	-4.39	Deleterious	0.999	Probably Damaging	0.969	Probably Damaging	1.33	Pathogenic	0.00	Affected			0.1405	0.1047		-3	-2	-8.3	43.03
c.980T>G	L327R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L327R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a destabilizing, pathogenic effect. All available predictions are concordant and indicate a likely pathogenic impact. Thus, based on the current computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.409189	Uncertain	0.939	0.490	0.000											-13.403	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.46	Destabilizing	0.3	4.75	Destabilizing	4.61	Destabilizing	1.95	Destabilizing	0.619	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.52	Pathogenic	0.00	Affected			0.1281	0.1085		-3	-2	-8.3	43.03
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.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.1196C>A	A399D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A399D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that agree on a pathogenic effect are REVEL, FoldX, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy methods give no definitive verdict: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable, and Foldetta is uncertain. Overall, the majority of available predictions (five pathogenic vs. four benign) lean toward pathogenicity. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125											-10.441	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.45	Destabilizing	0.2	1.17	Ambiguous	1.81	Ambiguous	0.91	Ambiguous	0.525	Likely Pathogenic	-1.84	Neutral	0.421	Benign	0.054	Benign	5.38	Benign	0.05	Affected			0.1533	0.1760		0	-2	-5.3	44.01
c.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.1343C>A	A448D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A448D 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 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods further support this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.292774	Uncertain	0.973	0.257	0.000											-17.290	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	8.13	Destabilizing	0.2	4.35	Destabilizing	6.24	Destabilizing	1.40	Destabilizing	0.662	Likely Pathogenic	-5.93	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.13	Benign	0.00	Affected			0.1541	0.1741		0	-2	-5.3	44.01
c.1382C>A	A461D 2D AIThe SynGAP1 missense variant A461D is not 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. The majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that A461D 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	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-14.918	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.89	Ambiguous	1.1	2.18	Destabilizing	1.54	Ambiguous	1.09	Destabilizing	0.477	Likely Benign	-5.47	Deleterious	0.997	Probably Damaging	0.792	Possibly Damaging	3.32	Benign	0.01	Affected			0.1533	0.2016		0	-2	-5.3	44.01
c.1406C>A	A469D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A469D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction from SIFT, and a consensus of pathogenic predictions from the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus). High‑accuracy methods further support a deleterious impact: 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) also indicates pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000					Uncertain		1				-14.643	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	5.09	Destabilizing	0.2	4.16	Destabilizing	4.63	Destabilizing	1.68	Destabilizing	0.738	Likely Pathogenic	-3.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.34	Pathogenic	0.21	Tolerated	3.37	34	0.1372	0.1583		0	-2	-5.3	44.01	237.0	-58.2	-0.2	0.1	0.8	0.1	X		X					Potentially Pathogenic	The methyl group of Ala469, located in an α helix (res. Ala461–Phe476), interacts with hydrophobic residues (e.g., Trp572, Leu588, Met470) in an inter-helix space formed by two other α helices (res. Glu582–Ser604, res. Arg563–Gly580). In the variant simulations, Asp469 introduces a negatively charged and bulky side chain into the hydrophobic niche. Consequently, the side chain of Asp469 rotates outward, allowing the carboxylate group to form a salt bridge with the guanidinium group of Arg575 on the protein surface. This interaction affects the continuity of the parent α helix (Ala461–Phe476). Due to the importance of hydrophobic packing, the structural effects could be more pronounced during actual protein folding.
c.1469C>A	A490D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity are unanimous: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 (HumDiv and HumVar), REVEL, premPS, FoldX, Rosetta, and Foldetta all classify the variant as pathogenic. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: 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. Based on the collective predictions, the variant is most likely pathogenic, and this assessment is consistent with the absence of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125											-16.643	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.1	4.23	Destabilizing	3.78	Destabilizing	1.33	Destabilizing	0.946	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.48	Pathogenic	0.00	Affected			0.1532	0.1741		0	-2	-5.3	44.01
c.1478C>A	A493D 2D AISynGAP1 missense variant A493D 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 substitution 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) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Consequently, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-16.834	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.45	Destabilizing	1.5	3.59	Destabilizing	4.02	Destabilizing	1.60	Destabilizing	0.925	Likely Pathogenic	-5.25	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.41	Pathogenic	0.01	Affected			0.1437	0.1541		0	-2	-5.3	44.01
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.1547C>A	A516D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A516D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, which scores the substitution as tolerated. In contrast, the majority of algorithms predict a pathogenic impact: 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). Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence indicates that A516D is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-14.621	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.65	Ambiguous	0.2	1.04	Ambiguous	0.85	Ambiguous	0.62	Ambiguous	0.725	Likely Pathogenic	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.15	Tolerated			0.1890	0.1679		0	-2	-5.3	44.01
c.1622C>A	A541D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A541D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT and FoldX, whereas a larger group—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. 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. Overall, the majority of evidence 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	0.050641	Structured	0.029947	Uncertain	0.955	0.365	0.000											-11.510	Likely Pathogenic	0.864	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.0	0.65	Ambiguous	0.51	Ambiguous	0.65	Ambiguous	0.571	Likely Pathogenic	-3.18	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.15	Pathogenic	0.14	Tolerated			0.1581	0.1902		0	-2	-5.3	44.01
c.1649C>A	A550D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A550D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect. Benign predictions: none. Pathogenic predictions: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. Uncertain predictions: Rosetta and Foldetta. 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 outputs, remains uncertain. Overall, the overwhelming majority of evidence indicates a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000											-18.844	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.51	Destabilizing	0.1	1.46	Ambiguous	1.99	Ambiguous	1.01	Destabilizing	0.879	Likely Pathogenic	-5.43	Deleterious	0.999	Probably Damaging	0.971	Probably Damaging	-1.32	Pathogenic	0.01	Affected			0.1333	0.1783		0	-2	-5.3	44.01
c.1709C>A	A570D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570D is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: 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. 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	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000											-14.117	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.47	Destabilizing	1.2	2.33	Destabilizing	2.40	Destabilizing	1.36	Destabilizing	0.805	Likely Pathogenic	-5.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.28	Pathogenic	0.03	Affected			0.2006	0.2206		0	-2	-5.3	44.01
c.1772C>A	A591D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591D 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 evaluated algorithms (AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, premPS, FoldX‑MD, Rosetta, Foldetta, and the SGM Consensus) uniformly predict a pathogenic or likely pathogenic outcome; FoldX‑MD is uncertain but does not counter the overall trend. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence 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	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000											-14.747	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.2	2.77	Destabilizing	2.16	Destabilizing	1.40	Destabilizing	0.414	Likely Benign	-5.02	Deleterious	0.919	Possibly Damaging	0.495	Possibly Damaging	3.42	Benign	0.00	Affected			0.1550	0.1741		0	-2	-5.3	44.01
c.17C>A	A6D 2D AIThe SynGAP1 missense variant A6D is reported in gnomAD (ID 6‑33420281‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.566480	Disordered	0.549054	Binding	0.377	0.920	0.875								6-33420281-C-A			-3.340	Likely Benign	0.210	Likely Benign	Likely Benign										0.211	Likely Benign	0.34	Neutral	0.117	Benign	0.010	Benign	4.07	Benign	0.00	Affected	4.32	1	0.1945	0.2530		-2	0	-5.3	44.01
c.1880C>A	A627D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A627D is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. All available evidence points to a damaging impact. Consequently, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000											-16.603	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	6.09	Destabilizing	1.3	5.83	Destabilizing	5.96	Destabilizing	1.58	Destabilizing	0.726	Likely Pathogenic	-5.93	Deleterious	0.999	Probably Damaging	0.961	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.1502	0.1816		0	-2	-5.3	44.01
c.1901C>A	A634D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634D is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree on 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 methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic effect. No predictions or stability results are missing or inconclusive. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-16.727	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.26	Destabilizing	0.5	4.24	Destabilizing	4.75	Destabilizing	1.79	Destabilizing	0.731	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1790	0.1816		0	-2	-5.3	44.01
c.2081C>A	A694D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A694D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the variant’s functional impact remains ambiguous. The predictions do not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-9.542	Likely Pathogenic	0.841	Likely Pathogenic	Ambiguous	0.35	Likely Benign	0.1	1.04	Ambiguous	0.70	Ambiguous	1.01	Destabilizing	0.163	Likely Benign	-2.47	Neutral	0.918	Possibly Damaging	0.375	Benign	3.48	Benign	0.05	Affected			0.2085	0.2216		0	-2	-5.3	44.01
c.2120C>A	A707D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools give uncertain results: premPS and Rosetta. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-9.160	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign	0.29	Likely Benign	0.0	-0.61	Ambiguous	-0.16	Likely Benign	0.89	Ambiguous	0.225	Likely Benign	-3.16	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.39	Benign	0.02	Affected			0.1376	0.1741		0	-2	-5.3	44.01
c.2171C>A	A724D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724D is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Four methods (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for A724D, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.233	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	0.2	0.86	Ambiguous	0.96	Ambiguous	0.60	Ambiguous	0.335	Likely Benign	-4.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1596	0.1812		0	-2	-5.3	44.01
c.2258C>A	A753D 2D AISynGAP1 missense variant A753D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score benign, while only polyPhen‑2 HumDiv predicts pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy tools corroborate this view: AlphaMissense‑Optimized reports a benign outcome, SGM‑Consensus likewise indicates Likely Benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign classification, and this conclusion does not contradict the ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.722781	Binding	0.381	0.873	0.625											-5.836	Likely Benign	0.408	Ambiguous	Likely Benign										0.113	Likely Benign	-1.66	Neutral	0.669	Possibly Damaging	0.265	Benign	2.60	Benign	0.60	Tolerated			0.2151	0.2200		0	-2	-5.3	44.01
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.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.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.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.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.2639C>A	A880D 2D AIThe SynGAP1 missense variant A880D is not reported 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. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely benign outcome, and no Foldetta stability result is available. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.621441	Binding	0.309	0.874	0.250											-4.571	Likely Benign	0.493	Ambiguous	Likely Benign										0.127	Likely Benign	-1.29	Neutral	0.918	Possibly Damaging	0.401	Benign	2.60	Benign	0.03	Affected			0.1664	0.1904		0	-2	-5.3	44.01
c.2663C>A	A888D 2D AIThe SynGAP1 missense variant A888D is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. 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 SIFT uniquely predicts it as pathogenic. The consensus prediction from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized reports benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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		0.784345	Disordered	0.575860	Binding	0.352	0.928	0.625											-3.870	Likely Benign	0.526	Ambiguous	Likely Benign										0.078	Likely Benign	-1.52	Neutral	0.077	Benign	0.097	Benign	2.56	Benign	0.00	Affected			0.1646	0.1386		0	-2	-5.3	44.01
c.2705C>A	A902D 2D AIThe SynGAP1 missense variant A902D is not reported 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. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, 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		0.675549	Disordered	0.517703	Binding	0.319	0.919	0.375											-5.273	Likely Benign	0.823	Likely Pathogenic	Ambiguous										0.101	Likely Benign	-1.21	Neutral	0.986	Probably Damaging	0.787	Possibly Damaging	2.59	Benign	0.00	Affected			0.1653	0.1609		0	-2	-5.3	44.01
c.2753C>A	A918D 2D AIThe SynGAP1 missense variant A918D is not reported 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. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradictory ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.891459	Binding	0.317	0.860	0.250											-4.281	Likely Benign	0.445	Ambiguous	Likely Benign										0.102	Likely Benign	-0.99	Neutral	0.961	Probably Damaging	0.721	Possibly Damaging	2.64	Benign	0.01	Affected			0.2037	0.2412		0	-2	-5.3	44.01
c.2804C>A	A935D 2D AIThe SynGAP1 missense variant A935D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—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 A935D, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.089	Likely Benign	0.817	Likely Pathogenic	Ambiguous										0.247	Likely Benign	-2.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1832	0.1860		0	-2	-5.3	44.01
c.2807C>A	A936D 2D AIThe SynGAP1 missense variant A936D is not 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, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. 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.			0.812494	Disordered	0.973218	Binding	0.319	0.874	0.625											-4.162	Likely Benign	0.686	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-1.63	Neutral	0.801	Possibly Damaging	0.339	Benign	2.48	Pathogenic	0.02	Affected			0.1778	0.1660		0	-2	-5.3	44.01
c.2930C>A	A977D 2D AIThe SynGAP1 missense variant A977D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign, while Foldetta’s protein‑folding stability assessment is unavailable. Overall, the majority of evidence points to a benign impact for A977D, 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		0.882776	Disordered	0.975330	Binding	0.306	0.884	0.625											-4.007	Likely Benign	0.717	Likely Pathogenic	Likely Benign										0.130	Likely Benign	-1.15	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	3.96	Benign	0.01	Affected			0.2253	0.2651		0	-2	-5.3	44.01
c.2990C>A	A997D 2D AIThe SynGAP1 missense variant A997D is not reported 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 for this variant. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.948624	Binding	0.273	0.901	0.500											-5.251	Likely Benign	0.319	Likely Benign	Likely Benign										0.131	Likely Benign	-1.09	Neutral	0.411	Benign	0.120	Benign	4.15	Benign	0.00	Affected			0.1815	0.2143		0	-2	-5.3	44.01
c.2993C>A	A998D 2D AIThe SynGAP1 missense variant A998D is not reported in ClinVar and has no entry in gnomAD. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy assessment indicates that AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome, and Foldetta data are unavailable. Overall, the majority of robust predictors lean toward a benign impact. Therefore, 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		0.759478	Disordered	0.951758	Binding	0.318	0.902	0.500											-5.481	Likely Benign	0.365	Ambiguous	Likely Benign										0.122	Likely Benign	-1.55	Neutral	0.971	Probably Damaging	0.690	Possibly Damaging	4.09	Benign	0.00	Affected			0.1754	0.2143		0	-2	-5.3	44.01
c.3134C>A	A1045D 2D AIThe SynGAP1 missense variant A1045D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the variant as benign. AlphaMissense‑Optimized also predicts a benign outcome, whereas AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” No tools predict pathogenicity. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective predictions strongly suggest that A1045D 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		0.975609	Disordered	0.948874	Binding	0.352	0.882	0.750											-5.734	Likely Benign	0.418	Ambiguous	Likely Benign										0.066	Likely Benign	-1.00	Neutral	0.411	Benign	0.172	Benign	2.64	Benign	0.16	Tolerated			0.1954	0.2102		0	-2	-5.3	44.01
c.3242C>A	A1081D 2D AIThe SynGAP1 missense variant A1081D is not reported 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 result is Uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.979759	Binding	0.288	0.895	0.750											-4.603	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-1.84	Neutral	0.611	Possibly Damaging	0.404	Benign	3.97	Benign	0.04	Affected			0.2069	0.2600		0	-2	-5.3	44.01
c.3305C>A	A1102D 2D AIThe SynGAP1 missense variant A1102D is not 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, and AlphaMissense‑Optimized. Only FATHMM 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 from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion 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.			0.915074	Disordered	0.962659	Binding	0.388	0.859	0.875											-4.647	Likely Benign	0.388	Ambiguous	Likely Benign										0.081	Likely Benign	-1.38	Neutral	0.033	Benign	0.028	Benign	2.27	Pathogenic	0.12	Tolerated			0.2045	0.2984		0	-2	-5.3	44.01
c.3449C>A	A1150D 2D AIThe SynGAP1 missense variant A1150D is not 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, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs. three 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 is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.762850	Disordered	0.795712	Binding	0.371	0.831	0.625											-3.923	Likely Benign	0.859	Likely Pathogenic	Ambiguous										0.156	Likely Benign	-2.30	Neutral	0.995	Probably Damaging	0.940	Probably Damaging	2.30	Pathogenic	0.01	Affected			0.1754	0.2143		0	-2	-5.3	44.01
c.3467C>A	A1156D 2D AIThe SynGAP1 missense variant A1156D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that A1156D is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.497	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.350	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.1662	0.2058		0	-2	-5.3	44.01
c.3497C>A	A1166D 2D AIThe SynGAP1 missense variant A1166D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (five benign vs. four pathogenic) and the consensus score lean toward a benign interpretation, with no conflict with ClinVar status. Thus, the variant is most likely benign, although the AlphaMissense‑Optimized prediction introduces some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.811691	Binding	0.381	0.803	0.375											-4.204	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.417	Likely Benign	-1.56	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	5.29	Benign	0.42	Tolerated			0.1709	0.2104		0	-2	-5.3	44.01
c.3512C>A	A1171D 2D AIThe SynGAP1 missense variant A1171D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” and Foldetta results are unavailable. Overall, the balance of evidence from multiple independent predictors and the SGM‑Consensus points to a benign impact for A1171D. 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	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500											-3.897	Likely Benign	0.814	Likely Pathogenic	Ambiguous										0.312	Likely Benign	-0.80	Neutral	0.611	Possibly Damaging	0.326	Benign	5.34	Benign	0.02	Affected			0.1952	0.2494		0	-2	-5.3	44.01
c.362C>A	A121D 2D AIThe SynGAP1 missense variant A121D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, 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 interpretation: 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 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		0.779859	Disordered	0.661304	Binding	0.362	0.888	0.750											-3.626	Likely Benign	0.595	Likely Pathogenic	Likely Benign										0.096	Likely Benign	-0.89	Neutral	0.244	Benign	0.050	Benign	4.06	Benign	0.03	Affected			0.1876	0.1945		0	-2	-5.3	44.01
c.368C>A	A123D 2D AIThe SynGAP1 missense variant A123D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the 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		0.521092	Disordered	0.689505	Binding	0.324	0.886	0.750											-3.515	Likely Benign	0.692	Likely Pathogenic	Likely Benign										0.168	Likely Benign	-1.17	Neutral	0.718	Possibly Damaging	0.218	Benign	4.15	Benign	0.01	Affected			0.2325	0.2893		0	-2	-5.3	44.01
c.3716C>A	A1239D 2D AIThe SynGAP1 missense variant A1239D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs. two pathogenic votes). Foldetta results are unavailable. Overall, the majority of evidence (six benign vs. three pathogenic predictions) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.541878	Disordered	0.534779	Binding	0.887	0.542	0.250											-6.177	Likely Benign	0.326	Likely Benign	Likely Benign										0.104	Likely Benign	-2.60	Deleterious	0.270	Benign	0.136	Benign	2.36	Pathogenic	0.00	Affected			0.1521	0.2062		0	-2	-5.3	44.01
c.3836C>A	A1279D 2D AIThe SynGAP1 missense variant A1279D is catalogued in gnomAD (ID 6‑33447884‑C‑A) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No pathogenic predictions are reported. Grouping by agreement, all available tools fall into the benign category, with no tools indicating pathogenicity. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from 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 result for this variant and is therefore considered unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.814139	Binding	0.485	0.724	0.750								6-33447884-C-A			-3.914	Likely Benign	0.172	Likely Benign	Likely Benign										0.087	Likely Benign	1.38	Neutral	0.000	Benign	0.000	Benign	2.89	Benign	0.35	Tolerated	3.77	5	0.1505	0.2062		-2	0	-5.3	44.01
c.3842C>A	A1281D 2D AIThe SynGAP1 missense variant A1281D is reported in gnomAD (ID 6‑33447890‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.821556	Binding	0.434	0.721	0.875								6-33447890-C-A			-5.183	Likely Benign	0.178	Likely Benign	Likely Benign										0.054	Likely Benign	-0.76	Neutral	0.901	Possibly Damaging	0.516	Possibly Damaging	2.68	Benign	0.15	Tolerated	4.32	4	0.2105	0.2462		-2	0	-5.3	44.01
c.3881C>A	A1294D 2D AIThe SynGAP1 missense variant A1294D is listed in gnomAD (ID 6‑33447929‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment further clarifies the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenicity. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of a benign ClinVar classification and the presence of the variant in a general population database. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625								6-33447929-C-A			-4.179	Likely Benign	0.369	Ambiguous	Likely Benign										0.224	Likely Benign	-4.17	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.14	Pathogenic	0.00	Affected	3.77	5	0.1893	0.2262		-2	0	-5.3	44.01
c.3935C>A	A1312D 2D AIThe SynGAP1 missense variant A1312D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence, particularly from the high‑accuracy tools, indicates that 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.			0.767246	Disordered	0.971112	Binding	0.392	0.902	0.750											-4.419	Likely Benign	0.398	Ambiguous	Likely Benign										0.272	Likely Benign	-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	3.11	Benign	0.00	Affected			0.2289	0.2993		0	-2	-5.3	44.01
c.3956C>A	A1319D 2D AIThe SynGAP1 missense variant A1319D is reported in gnomAD (ID 6‑33451830‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the same four tools) is benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for A1319D, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.960481	Binding	0.454	0.851	0.750								6-33451830-C-A			-5.156	Likely Benign	0.297	Likely Benign	Likely Benign										0.208	Likely Benign	-0.85	Neutral	0.971	Probably Damaging	0.813	Possibly Damaging	4.08	Benign	0.01	Affected	3.77	5	0.2290	0.2702		-2	0	-5.3	44.01
c.3965C>A	A1322D 2D AIThe SynGAP1 missense variant A1322D is catalogued in gnomAD (ID 6‑33451839‑C‑A) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No pathogenic predictions are reported. Grouping by consensus, all available tools fall into the benign category, with no tools indicating pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no result for this variant, so its status is unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.921040	Binding	0.466	0.825	0.875								6-33451839-C-A			-5.744	Likely Benign	0.284	Likely Benign	Likely Benign										0.092	Likely Benign	0.70	Neutral	0.013	Benign	0.004	Benign	4.17	Benign	0.45	Tolerated	3.77	5	0.2246	0.3134		-2	0	-5.3	44.01
c.497C>A	A166D 2D AIThe SynGAP1 missense variant A166D is not 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. The high‑accuracy consensus method SGM (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, yielding a 2‑to‑2 split. AlphaMissense‑Optimized rates the variant as uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this change. Overall, the majority of tools predict a pathogenic impact, and there is no ClinVar annotation to contradict this assessment. 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.			0.425610	Structured	0.505037	Binding	0.384	0.658	0.125											-12.171	Likely Pathogenic	0.900	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-2.21	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	4.02	Benign	0.01	Affected			0.2031	0.2694		0	-2	-5.3	44.01
c.512C>A	A171D 2D AIThe SynGAP1 missense variant A171D is not reported in ClinVar and has no entries 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. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments therefore lean toward a benign interpretation: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is benign, and Foldetta data are missing. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.562014	Disordered	0.492272	Uncertain	0.358	0.652	0.375											-6.977	Likely Benign	0.908	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-1.45	Neutral	0.244	Benign	0.037	Benign	4.15	Benign	0.01	Affected			0.1634	0.2462		0	-2	-5.3	44.01
c.56C>A	A19D 2D AIThe SynGAP1 missense variant A19D is listed in gnomAD (ID 6‑33420320‑C‑A) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, 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		0.529623	Disordered	0.443393	Uncertain	0.378	0.906	0.500								6-33420320-C-A	2	1.30e-6	-3.746	Likely Benign	0.573	Likely Pathogenic	Likely Benign										0.055	Likely Benign	-0.08	Neutral	0.588	Possibly Damaging	0.054	Benign	4.07	Benign	0.00	Affected	4.32	1	0.2508	0.2734		-2	0	-5.3	44.01
c.578C>A	A193D 2D AIThe SynGAP1 missense variant A193D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also yields a pathogenic consensus. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that A193D is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-7.488	In-Between	0.998	Likely Pathogenic	Likely Pathogenic										0.217	Likely Benign	-3.46	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.99	Benign	0.01	Affected			0.1688	0.1835		0	-2	-5.3	44.01
c.695C>A	A232D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A232D 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, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Uncertain or inconclusive results are reported for Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as pathogenic, while Foldetta remains uncertain. Overall, the majority of available predictions support a pathogenic impact. Thus, 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	PH	0.254060	Structured	0.307228	Uncertain	0.878	0.305	0.000											-13.956	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.14	Likely Benign	0.2	1.55	Ambiguous	0.85	Ambiguous	0.77	Ambiguous	0.725	Likely Pathogenic	-2.50	Deleterious	0.845	Possibly Damaging	0.348	Benign	5.78	Benign	0.02	Affected			0.2066	0.2896		0	-2	-5.3	44.01
c.710C>A	A237D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A237D is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, while the remaining tools—SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict pathogenicity. Two tools, FoldX and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a deleterious impact: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenicity, AlphaMissense‑Optimized is uncertain, and Foldetta predicts a destabilizing, pathogenic effect. Overall, the evidence overwhelmingly indicates that the variant is pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.200174	Structured	0.334699	Uncertain	0.719	0.352	0.000											-8.880	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	1.23	Ambiguous	0.4	3.49	Destabilizing	2.36	Destabilizing	1.20	Destabilizing	0.769	Likely Pathogenic	-3.97	Deleterious	0.969	Probably Damaging	0.704	Possibly Damaging	5.88	Benign	0.05	Affected			0.1419	0.2302		0	-2	-5.3	44.01
c.812C>A	A271D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271D is listed in ClinVar as Pathogenic (ClinVar ID 2019732.0) and is not reported in gnomAD. Prediction tools that assess functional impact uniformly classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125					Pathogenic		1				-18.590	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.71	Destabilizing	0.4	2.67	Destabilizing	3.69	Destabilizing	1.59	Destabilizing	0.706	Likely Pathogenic	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.62	Pathogenic	0.00	Affected	3.38	19	0.1565	0.1541		0	-2	-5.3	44.01	226.2	-63.4	0.0	0.0	0.9	0.1	X		X	X			X	Potentially Pathogenic	The methyl group of Ala271, located near the end of an anti-parallel β sheet strand (res. Arg259-Arg272), packs against multiple hydrophobic residues such as Val400, Val306, and Leu274 in the WT simulations. In the variant simulations, the carboxylate group of Asp271 is not suitable for the hydrophobic niche, causing the hydrophobic residues to make room for the swapped residue. Additionally, the carboxylate group of the Asp271 side chain forms hydrogen bonds with the backbone amide groups of Arg272 and Ala399 in the β sheet, or even forms a salt bridge with the amino group of the Lys394 side chain. This directly affects the integrity of the anti-parallel β sheet at the end. In short, the residue swap disrupts the C2 domain packing during folding, which could weaken the stability of the SynGAP-membrane association.
c.902C>A	A301D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM all predict benign, whereas polyPhen‑2 (HumDiv and HumVar) and ESM1b predict pathogenic. Tools with uncertain outputs—Rosetta, Foldetta, and AlphaMissense‑Default—do not provide decisive evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains inconclusive. Taken together, the preponderance of evidence indicates that A301D is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-10.276	Likely Pathogenic	0.488	Ambiguous	Likely Benign	-0.37	Likely Benign	0.2	-1.15	Ambiguous	-0.76	Ambiguous	0.23	Likely Benign	0.224	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.17	Benign	0.07	Tolerated			0.1599	0.1705		0	-2	-5.3	44.01
c.956C>A	A319D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A319D missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus remains pathogenic. Foldetta, which integrates FoldX‑MD (benign) and Rosetta (uncertain), is considered unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125											-11.144	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign	-0.02	Likely Benign	0.2	-0.84	Ambiguous	-0.43	Likely Benign	0.30	Likely Benign	0.373	Likely Benign	-2.38	Neutral	0.998	Probably Damaging	0.966	Probably Damaging	2.01	Pathogenic	0.20	Tolerated			0.1504	0.1360		0	-2	-5.3	44.01
c.965C>A	A322D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A322D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The remaining tools—FoldX, Rosetta, ESM1b, and AlphaMissense‑Default—return uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta indicates no significant stability change (uncertain). Overall, the preponderance of evidence (seven benign predictions versus one pathogenic) suggests 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.		C2	0.175930	Structured	0.425745	Uncertain	0.938	0.334	0.000											-7.184	In-Between	0.411	Ambiguous	Likely Benign	0.65	Ambiguous	0.1	1.35	Ambiguous	1.00	Ambiguous	0.34	Likely Benign	0.246	Likely Benign	-0.95	Neutral	0.270	Benign	0.136	Benign	1.96	Pathogenic	0.32	Tolerated			0.1646	0.1660		0	-2	-5.3	44.01
c.1190G>T	C397F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397F is reported in gnomAD (6-33438095-G-T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, Rosetta, and the protein‑folding stability method Foldetta. FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, while Foldetta indicates a pathogenic effect. Because the majority of tools (nine benign vs. four pathogenic) lean toward a benign outcome and the high‑accuracy consensus is split, the variant is most likely benign. 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 Benign	C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250								6-33438095-G-T	1	6.20e-7	-6.571	Likely Benign	0.194	Likely Benign	Likely Benign	1.31	Ambiguous	1.7	3.61	Destabilizing	2.46	Destabilizing	0.12	Likely Benign	0.493	Likely Benign	-1.95	Neutral	0.952	Possibly Damaging	0.497	Possibly Damaging	4.65	Benign	0.07	Tolerated	3.41	15	0.1426	0.5231		-2	-4	0.3	44.04
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.146G>T	C49F 2D AIThe SynGAP1 missense variant C49F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while 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: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—classifies the variant as pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-7.194	In-Between	0.893	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-3.21	Deleterious	0.676	Possibly Damaging	0.695	Possibly Damaging	3.86	Benign	0.00	Affected			0.1199	0.3690		-4	-2	0.3	44.04
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.1592G>T	C531F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Rosetta and polyPhen‑2 HumVar, while the majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Tools with inconclusive or uncertain results are AlphaMissense‑Optimized, Foldetta, and premPS. High‑accuracy assessments show SGM‑Consensus as “Likely Pathogenic”; AlphaMissense‑Optimized is uncertain; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also uncertain. Taken together, the preponderance of evidence from multiple pathogenic‑predicting algorithms and the SGM‑Consensus score indicates that the variant is most likely pathogenic. 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	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-10.428	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	2.47	Destabilizing	1.6	0.26	Likely Benign	1.37	Ambiguous	0.59	Ambiguous	0.519	Likely Pathogenic	-8.89	Deleterious	0.866	Possibly Damaging	0.244	Benign	-1.23	Pathogenic	0.01	Affected			0.1103	0.3784		-4	-2	0.3	44.04
c.1637G>T	C546F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C546F is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the variant as benign include premPS and SIFT, whereas the majority of tools predict pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for C546F, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-13.479	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	-1.21	Ambiguous	0.9	3.98	Destabilizing	1.39	Ambiguous	0.34	Likely Benign	0.800	Likely Pathogenic	-8.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.20	Pathogenic	0.12	Tolerated			0.1622	0.3533		-4	-2	0.3	44.04
c.1640G>T	C547F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from premPS, while all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify it as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a destabilizing, pathogenic effect. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions and the absence of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-15.404	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	5.63	Destabilizing	1.2	5.82	Destabilizing	5.73	Destabilizing	0.49	Likely Benign	0.828	Likely Pathogenic	-10.57	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.29	Pathogenic	0.05	Affected			0.1603	0.3260		-4	-2	0.3	44.04
c.1655G>T	C552F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. FoldX and Foldetta give uncertain results. High‑accuracy methods specifically report AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. 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 entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-14.979	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-1.01	Ambiguous	0.1	-0.35	Likely Benign	-0.68	Ambiguous	0.40	Likely Benign	0.759	Likely Pathogenic	-9.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.07	Tolerated			0.1209	0.3081		-4	-2	0.3	44.04
c.1676G>T	C559F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559F is not reported in ClinVar (ClinVar ID = None) and has no entry in gnomAD (gnomAD ID = None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, 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 (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the predictions are split evenly, but the two most reliable tools (AlphaMissense‑Optimized and Foldetta) both indicate a benign effect, whereas the consensus pathogenic tool is a single outlier. Thus, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-13.194	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-0.43	Likely Benign	0.0	-0.04	Likely Benign	-0.24	Likely Benign	0.29	Likely Benign	0.576	Likely Pathogenic	-8.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.43	Benign	0.09	Tolerated			0.2234	0.2653		-4	-2	0.3	44.04
c.1727G>T	C576F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576F is not reported in ClinVar (ClinVar ID = None) and has no entries in gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—consistently predict a pathogenic or likely pathogenic impact. Uncertain predictions from Rosetta and premPS are treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic; 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 pathogenic. Based on the overwhelming agreement among high‑confidence tools, the variant is most likely pathogenic, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-13.467	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	5.04	Destabilizing	0.5	1.81	Ambiguous	3.43	Destabilizing	0.58	Ambiguous	0.516	Likely Pathogenic	-9.93	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.40	Benign	0.02	Affected			0.1626	0.3527		-4	-2	0.3	44.04
c.1796G>T	C599F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599F is not reported in ClinVar (ClinVar ID None) and has no entry 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 or likely pathogenic. Only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: 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) also predicts pathogenic. No prediction or folding‑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	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.969	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	3.72	Destabilizing	1.3	2.70	Destabilizing	3.21	Destabilizing	-0.42	Likely Benign	0.902	Likely Pathogenic	-10.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.47	Pathogenic	0.00	Affected			0.1319	0.3073		-4	-2	0.3	44.04
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.656G>T	C219F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219F 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 premPS and FATHMM, while the remaining 13 tools—including SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among the majority of tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000											-14.322	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.31	Destabilizing	1.9	2.45	Destabilizing	4.88	Destabilizing	0.47	Likely Benign	0.814	Likely Pathogenic	-9.18	Deleterious	0.940	Possibly Damaging	0.505	Possibly Damaging	5.82	Benign	0.00	Affected			0.0959	0.3804		-4	-2	0.3	44.04
c.689G>T	C230F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Foldetta and premPS give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; Foldetta remains uncertain. Overall, the preponderance of evidence indicates that C230F 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	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-11.134	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	-0.09	Likely Benign	0.1	-2.03	Stabilizing	-1.06	Ambiguous	0.51	Ambiguous	0.840	Likely Pathogenic	-8.73	Deleterious	0.940	Possibly Damaging	0.641	Possibly Damaging	5.96	Benign	0.03	Affected			0.1329	0.4173		-4	-2	0.3	44.04
c.698G>T	C233F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include Rosetta, premPS, and FATHMM, whereas the remaining tools—REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, and Foldetta—predict a pathogenic or likely pathogenic impact. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence supports a pathogenic effect, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-14.564	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	9.36	Destabilizing	3.0	-0.19	Likely Benign	4.59	Destabilizing	0.37	Likely Benign	0.901	Likely Pathogenic	-9.79	Deleterious	0.940	Possibly Damaging	0.459	Possibly Damaging	5.73	Benign	0.00	Affected			0.1524	0.5231		-4	-2	0.3	44.04
c.845G>T	C282F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282F is not listed in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are provided by REVEL and premPS, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic outcome. Taken together, the overwhelming majority of evidence points to a pathogenic impact for C282F. This conclusion is consistent with the absence of a ClinVar entry, which does not contradict the prediction. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-13.288	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	6.22	Destabilizing	1.4	2.38	Destabilizing	4.30	Destabilizing	0.42	Likely Benign	0.430	Likely Benign	-10.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.1267	0.3607		-4	-2	0.3	44.04
c.854G>T	C285F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome; Foldetta is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence (12 pathogenic vs. 3 benign 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	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.397	Likely Pathogenic	0.716	Likely Pathogenic	Likely Benign	3.27	Destabilizing	1.1	-1.72	Ambiguous	0.78	Ambiguous	0.35	Likely Benign	0.500	Likely Pathogenic	-8.84	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.12	Tolerated			0.1626	0.4007		-4	-2	0.3	44.04
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.1030G>T	G344C 2D AIThe SynGAP1 missense variant G344C is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic outcome include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy methods specifically show pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No tool predicts a benign effect. Based on the unanimous pathogenic predictions and the absence of any ClinVar or gnomAD evidence, 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	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250											-12.880	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	8.52	Destabilizing	2.9	7.52	Destabilizing	8.02	Destabilizing	0.59	Ambiguous	0.794	Likely Pathogenic	-8.02	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.47	Pathogenic	0.01	Affected			0.1184	0.4788		-3	-3	2.9	46.09
c.1108G>T	G370C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G370C has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from REVEL, FoldX, Rosetta, Foldetta, and FATHMM. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction or stability result is missing. Overall, the majority of tools predict a benign effect, and the high‑accuracy consensus also leans benign, while only one high‑accuracy method (Foldetta) suggests pathogenicity. Thus, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.461924	Structured	0.434325	Uncertain	0.359	0.720	0.500											-7.071	In-Between	0.119	Likely Benign	Likely Benign	3.01	Destabilizing	2.1	2.03	Destabilizing	2.52	Destabilizing	0.29	Likely Benign	0.511	Likely Pathogenic	-1.00	Neutral	0.353	Benign	0.010	Benign	1.32	Pathogenic	0.06	Tolerated			0.1245	0.4412		-3	-3	2.9	46.09
c.1126G>T	G376C 2D AISynGAP1 missense variant G376C is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, premPS, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls come from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools report uncertainty: Foldetta and ESM1b. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, whereas the most accurate methods favor a benign effect. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625					Uncertain		1				-7.686	In-Between	0.125	Likely Benign	Likely Benign	2.56	Destabilizing	0.5	0.22	Likely Benign	1.39	Ambiguous	0.16	Likely Benign	0.560	Likely Pathogenic	-1.15	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1476	0.3929		-3	-3	2.9	46.09
c.1132G>T	G378C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G378C is 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, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools (8/12) predict pathogenicity, and the high‑accuracy consensus leans toward benign only for AlphaMissense‑Optimized and SGM Consensus, while Foldetta indicates instability. Thus, the variant is most likely pathogenic based on the preponderance of evidence, 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.		C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625											-7.981	In-Between	0.203	Likely Benign	Likely Benign	7.63	Destabilizing	2.7	12.14	Destabilizing	9.89	Destabilizing	0.26	Likely Benign	0.635	Likely Pathogenic	-1.18	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1595	0.4240		-3	-3	2.9	46.09
c.1150G>T	G384C 2D AIThe SynGAP1 missense variant G384C is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenic; and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split and is treated as unavailable. Overall, the majority of predictions (seven pathogenic vs. five benign) and the pathogenic Foldetta result indicate that the variant is most likely pathogenic, with no contradiction to ClinVar status because the variant is not yet classified there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750											-8.363	Likely Pathogenic	0.135	Likely Benign	Likely Benign	2.41	Destabilizing	2.0	5.50	Destabilizing	3.96	Destabilizing	0.17	Likely Benign	0.456	Likely Benign	-1.07	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1530	0.4240		-3	-3	2.9	46.09
c.1159G>T	G387C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G387C is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438064‑G‑T). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, SIFT, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of high‑confidence tools lean toward a benign interpretation, and this does not contradict the ClinVar status, which has no pathogenic classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.642678	Disordered	0.422910	Uncertain	0.293	0.861	0.750								6-33438064-G-T	1	6.21e-7	-7.609	In-Between	0.146	Likely Benign	Likely Benign	2.88	Destabilizing	0.6	2.34	Destabilizing	2.61	Destabilizing	-0.03	Likely Benign	0.430	Likely Benign	-0.58	Neutral	0.859	Possibly Damaging	0.346	Benign	1.32	Pathogenic	0.01	Affected	4.32	3	0.1589	0.4240		-3	-3	2.9	46.09
c.1162G>T	G388C 2D 3DClick to see structure in 3D Viewer AISynGAP1 G388C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and PROVEAN, while pathogenic predictions arise from REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized predicts benign, Foldetta predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Because the majority of evidence points to pathogenicity and there is no ClinVar entry to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750											-8.088	Likely Pathogenic	0.121	Likely Benign	Likely Benign	4.01	Destabilizing	3.7	4.95	Destabilizing	4.48	Destabilizing	0.03	Likely Benign	0.603	Likely Pathogenic	-0.98	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1497	0.4112		-3	-3	2.9	46.09
c.1171G>T	G391C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G391C 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 AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and PROVEAN, whereas the remaining tools—REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—predict it to be pathogenic. 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 evidence points to a pathogenic effect. This prediction 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	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750											-8.596	Likely Pathogenic	0.123	Likely Benign	Likely Benign	2.65	Destabilizing	0.7	5.03	Destabilizing	3.84	Destabilizing	0.11	Likely Benign	0.640	Likely Pathogenic	-1.29	Neutral	1.000	Probably Damaging	0.970	Probably Damaging	1.32	Pathogenic	0.03	Affected			0.1483	0.4225		-3	-3	2.9	46.09
c.1177G>T	G393C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G393C is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, premPS, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus (likely pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain (no definitive stability change). The majority of evidence points toward a pathogenic effect, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625											-8.854	Likely Pathogenic	0.181	Likely Benign	Likely Benign	2.99	Destabilizing	0.9	-0.26	Likely Benign	1.37	Ambiguous	0.43	Likely Benign	0.769	Likely Pathogenic	-3.05	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.1593	0.4408		-3	-3	2.9	46.09
c.1186G>T	G396C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G396C is not 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; premPS is uncertain. The high‑accuracy consensus methods give a mixed signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the majority of individual predictors and the SGM‑Consensus lean toward a benign interpretation, and the two high‑accuracy tools that are available also favor benign over pathogenic. Therefore, 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.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500											-5.459	Likely Benign	0.115	Likely Benign	Likely Benign	2.15	Destabilizing	0.7	2.52	Destabilizing	2.34	Destabilizing	0.59	Ambiguous	0.411	Likely Benign	-3.00	Deleterious	0.983	Probably Damaging	0.533	Possibly Damaging	3.89	Benign	0.08	Tolerated			0.1181	0.4541		-3	-3	2.9	46.09
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.1327G>T	G443C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools are inconclusive: Foldetta is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta remains uncertain. Overall, the consensus of the majority of evidence points to a benign impact for G443C, 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	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-4.308	Likely Benign	0.208	Likely Benign	Likely Benign	-0.06	Likely Benign	0.0	-0.95	Ambiguous	-0.51	Ambiguous	-0.10	Likely Benign	0.260	Likely Benign	-2.94	Deleterious	0.977	Probably Damaging	0.504	Possibly Damaging	3.37	Benign	0.16	Tolerated			0.1258	0.2782		-3	-3	2.9	46.09
c.1375G>T	G459C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G459C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of algorithms (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence points to a pathogenic effect for G459C, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-12.109	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	2.46	Destabilizing	0.2	1.49	Ambiguous	1.98	Ambiguous	0.65	Ambiguous	0.586	Likely Pathogenic	-8.46	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.00	Benign	0.00	Affected			0.0960	0.4103		-3	-3	2.9	46.09
c.1504G>T	G502C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502C lies 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 only premPS. The majority of tools predict a pathogenic effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Tools with uncertain or inconclusive outputs are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. Overall, the preponderance of evidence points to a pathogenic impact for G502C, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000											-12.086	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	1.02	Ambiguous	0.5	1.55	Ambiguous	1.29	Ambiguous	0.30	Likely Benign	0.845	Likely Pathogenic	-8.65	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	-1.67	Pathogenic	0.00	Affected			0.1279	0.2691		-3	-3	2.9	46.09
c.1738G>T	G580C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic outcome include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta and premPS. High‑accuracy methods all support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No tool predicts benign. **Based on the consensus of available predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-11.608	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.94	Destabilizing	0.1	1.18	Ambiguous	2.06	Destabilizing	0.60	Ambiguous	0.755	Likely Pathogenic	-8.66	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.18	Pathogenic	0.01	Affected			0.1422	0.2146		-3	-3	2.9	46.09
c.1939G>T	G647C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647C is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, the majority (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) uniformly predict a benign effect, whereas only SIFT classifies the change as pathogenic. High‑accuracy tools give consistent benign results: 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) reports a benign stability change. No prediction or folding‑stability result is missing or inconclusive. Based on the collective 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	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-2.955	Likely Benign	0.112	Likely Benign	Likely Benign	0.41	Likely Benign	0.0	-0.20	Likely Benign	0.11	Likely Benign	0.05	Likely Benign	0.112	Likely Benign	-1.63	Neutral	0.003	Benign	0.004	Benign	3.44	Benign	0.02	Affected			0.1194	0.3250		-3	-3	2.9	46.09
c.1972G>T	G658C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. One tool, ESM1b, yields an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign (2 benign vs. 1 pathogenic, 1 uncertain), and Foldetta predicts a benign impact on protein stability. Overall, the majority of evidence points to a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-7.577	In-Between	0.170	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	0.04	Likely Benign	0.05	Likely Benign	0.46	Likely Benign	0.146	Likely Benign	-3.49	Deleterious	0.989	Probably Damaging	0.544	Possibly Damaging	3.37	Benign	0.04	Affected			0.1509	0.3141		-3	-3	2.9	46.09
c.2041G>T	G681C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681C is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all classify it as pathogenic, while only FATHMM predicts a benign outcome. Uncertain calls come from FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta) is pathogenic, and AlphaMissense‑Optimized remains inconclusive. Overall, the evidence strongly favors a pathogenic interpretation, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.374	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.89	Ambiguous	1.3	2.63	Destabilizing	2.26	Destabilizing	0.66	Ambiguous	0.554	Likely Pathogenic	-8.98	Deleterious	1.000	Probably Damaging	0.959	Probably Damaging	3.33	Benign	0.00	Affected			0.1194	0.3886		-3	-3	2.9	46.09
c.2056G>T	G686C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, FATHMM, and the protein‑folding stability method Foldetta; pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, with the SGM‑Consensus score labeling the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-12.790	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.2	0.41	Likely Benign	0.33	Likely Benign	0.93	Ambiguous	0.553	Likely Pathogenic	-8.14	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	3.31	Benign	0.02	Affected			0.1209	0.3246		-3	-3	2.9	46.09
c.2134G>T	G712C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712C is catalogued in gnomAD (6‑33441599‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000								6-33441599-G-T	1	6.20e-7	-11.376	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous	2.54	Destabilizing	0.0	5.72	Destabilizing	4.13	Destabilizing	0.56	Ambiguous	0.516	Likely Pathogenic	-7.75	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.00	Affected	3.50	9	0.1513	0.3947		-3	-3	2.9	46.09
c.2269G>T	G757C 2D AIThe SynGAP1 missense variant G757C 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 show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this 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		0.436924	Structured	0.830995	Binding	0.310	0.869	0.375											-6.652	Likely Benign	0.139	Likely Benign	Likely Benign										0.179	Likely Benign	-1.74	Neutral	0.997	Probably Damaging	0.870	Possibly Damaging	2.65	Benign	0.04	Affected			0.1302	0.3630		-3	-3	2.9	46.09
c.2326G>T	G776C 2D AIThe SynGAP1 missense variant G776C is not reported in ClinVar but is present in gnomAD (ID 6‑33442484‑G‑T). Prediction tools cluster into benign (REVEL, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). Two tools (ESM1b, AlphaMissense‑Default) return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the single high‑accuracy tool suggests benign. Given the preponderance of pathogenic predictions and the absence of a ClinVar entry, the variant is most likely pathogenic and does not contradict any existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442484-G-T			-7.974	In-Between	0.380	Ambiguous	Likely Benign										0.181	Likely Benign	-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	4.15	Benign	0.01	Affected	3.64	6	0.1235	0.4403		-3	-3	2.9	46.09
c.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.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.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.2542G>T	G848C 2D AIThe SynGAP1 missense variant G848C 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 computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500											-6.987	Likely Benign	0.248	Likely Benign	Likely Benign										0.237	Likely Benign	-1.14	Neutral	0.998	Probably Damaging	0.922	Probably Damaging	2.55	Benign	0.01	Affected			0.1264	0.4400		-3	-3	2.9	46.09
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.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.2686G>T	G896C 2D AIThe SynGAP1 missense variant G896C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625											-5.607	Likely Benign	0.245	Likely Benign	Likely Benign										0.193	Likely Benign	-2.59	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.50	Benign	0.10	Tolerated			0.1270	0.4369		-3	-3	2.9	46.09
c.2707G>T	G903C 2D AIThe SynGAP1 missense variant G903C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain and does not influence the consensus. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, which would provide a protein‑folding stability estimate, is unavailable for this variant. Overall, the majority of evidence (five pathogenic versus three benign predictions) points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375											-6.593	Likely Benign	0.471	Ambiguous	Likely Benign										0.151	Likely Benign	-3.28	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	2.32	Pathogenic	0.02	Affected			0.1158	0.4420		-3	-3	2.9	46.09
c.2728G>T	G910C 2D AIThe SynGAP1 missense variant G910C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta data are unavailable. Overall, the majority of tools (five pathogenic vs four benign) lean toward a pathogenic interpretation, and the high‑accuracy benign prediction from AlphaMissense‑Optimized does not override this trend. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250											-6.359	Likely Benign	0.723	Likely Pathogenic	Likely Benign										0.252	Likely Benign	-3.11	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.69	Benign	0.01	Affected			0.1179	0.4194		-3	-3	2.9	46.09
c.2743G>T	G915C 2D AIThe SynGAP1 missense variant G915C is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6-33443295-G‑T). Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) 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 the ClinVar status, which currently has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.808641	Binding	0.302	0.880	0.375								6-33443295-G-T	1	6.20e-7	-6.446	Likely Benign	0.185	Likely Benign	Likely Benign										0.103	Likely Benign	-2.84	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.64	Benign	0.01	Affected	3.77	5	0.1023	0.4471		-3	-3	2.9	46.09
c.2818G>T	G940C 2D AIThe SynGAP1 missense variant G940C is 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, 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 results are not available. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this conclusion, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625											-8.158	Likely Pathogenic	0.097	Likely Benign	Likely Benign										0.089	Likely Benign	-0.40	Neutral	0.996	Probably Damaging	0.905	Possibly Damaging	2.70	Benign	0.11	Tolerated			0.1307	0.4354		-3	-3	2.9	46.09
c.2827G>T	G943C 2D AIThe SynGAP1 missense variant G943C is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which itself is “Likely Benign”). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b all predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy tools—points to a benign impact. Thus, 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		0.973328	Disordered	0.860437	Binding	0.372	0.910	0.750											-9.822	Likely Pathogenic	0.108	Likely Benign	Likely Benign										0.356	Likely Benign	-0.94	Neutral	0.938	Possibly Damaging	0.649	Possibly Damaging	2.84	Benign	0.10	Tolerated			0.1425	0.4439		-3	-3	2.9	46.09
c.2830G>T	G944C 2D AIThe SynGAP1 missense variant G944C is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443382‑G‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote of the four contributing 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 evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750								6-33443382-G-T	1	6.20e-7	-9.121	Likely Pathogenic	0.093	Likely Benign	Likely Benign										0.426	Likely Benign	-1.79	Neutral	0.975	Probably Damaging	0.848	Possibly Damaging	3.70	Benign	0.00	Affected	4.32	4	0.1399	0.4439		-3	-3	2.9	46.09
c.2842G>T	G948C 2D AIThe SynGAP1 missense variant G948C is not reported 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) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar assertion exists for this variant. Thus, based on the available computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750											-10.254	Likely Pathogenic	0.102	Likely Benign	Likely Benign										0.247	Likely Benign	-0.77	Neutral	0.997	Probably Damaging	0.840	Possibly Damaging	4.50	Benign	0.04	Affected			0.1422	0.4439		-3	-3	2.9	46.09
c.2845G>T	G949C 2D AIThe SynGAP1 missense variant G949C is not 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 takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750											-10.580	Likely Pathogenic	0.091	Likely Benign	Likely Benign										0.345	Likely Benign	-1.02	Neutral	1.000	Probably Damaging	0.975	Probably Damaging	2.21	Pathogenic	0.01	Affected			0.1480	0.4097		-3	-3	2.9	46.09
c.2848G>T	G950C 2D AIThe SynGAP1 missense variant G950C is not 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, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (five pathogenic vs. four benign) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.888649	Binding	0.368	0.923	0.750											-9.589	Likely Pathogenic	0.092	Likely Benign	Likely Benign										0.395	Likely Benign	-0.35	Neutral	0.983	Probably Damaging	0.750	Possibly Damaging	2.26	Pathogenic	0.01	Affected			0.1406	0.4439		-3	-3	2.9	46.09
c.2854G>T	G952C 2D AIThe SynGAP1 missense variant G952C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.910621	Binding	0.341	0.926	0.750											-8.599	Likely Pathogenic	0.088	Likely Benign	Likely Benign										0.272	Likely Benign	-0.18	Neutral	0.371	Benign	0.169	Benign	3.20	Benign	0.01	Affected			0.1458	0.4439		-3	-3	2.9	46.09
c.286G>T	G96C 2D AIThe SynGAP1 missense variant G96C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods give a benign verdict: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No result is available from Foldetta, so its folding‑stability assessment is not considered. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of any ClinVar classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.599491	Binding	0.335	0.871	0.625											-5.140	Likely Benign	0.087	Likely Benign	Likely Benign										0.112	Likely Benign	-1.87	Neutral	0.981	Probably Damaging	0.216	Benign	4.12	Benign	0.00	Affected			0.1645	0.4142		-3	-3	2.9	46.09
c.2902G>T	G968C 2D AIThe SynGAP1 missense variant G968C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. 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 exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750											-8.441	Likely Pathogenic	0.117	Likely Benign	Likely Benign										0.170	Likely Benign	-0.99	Neutral	0.992	Probably Damaging	0.820	Possibly Damaging	4.12	Benign	0.07	Tolerated			0.1294	0.4768		-3	-3	2.9	46.09
c.2941G>T	G981C 2D AIThe SynGAP1 missense variant G981C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic 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; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for G981C, 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		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625											-5.646	Likely Benign	0.593	Likely Pathogenic	Likely Benign										0.228	Likely Benign	-1.81	Neutral	1.000	Probably Damaging	0.992	Probably Damaging	3.72	Benign	0.00	Affected			0.1398	0.4593		-3	-3	2.9	46.09
c.3040G>T	G1014C 2D AIThe SynGAP1 G1014C missense variant 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. 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. 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		0.771762	Disordered	0.914808	Binding	0.293	0.835	0.625											-7.424	In-Between	0.151	Likely Benign	Likely Benign										0.089	Likely Benign	-2.49	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	2.68	Benign	0.06	Tolerated			0.1401	0.4126		-3	-3	2.9	46.09
c.307G>T	G103C 2D AIThe SynGAP1 missense variant G103C 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. Overall, the majority of evidence points to a benign effect for G103C, 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		0.795062	Disordered	0.687376	Binding	0.381	0.877	0.625											-5.681	Likely Benign	0.136	Likely Benign	Likely Benign										0.128	Likely Benign	-1.12	Neutral	0.995	Probably Damaging	0.829	Possibly Damaging	4.17	Benign	0.00	Affected			0.1494	0.3767		-3	-3	2.9	46.09
c.3118G>T	G1040C 2D AIThe SynGAP1 missense variant G1040C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict pathogenicity, while ESM1b and AlphaMissense‑Optimized 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 further support this view: AlphaMissense‑Optimized reports a benign prediction, whereas the SGM‑Consensus remains Likely Pathogenic; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-6.272	Likely Benign	0.620	Likely Pathogenic	Likely Benign										0.744	Likely Pathogenic	-3.04	Deleterious	0.999	Probably Damaging	0.917	Probably Damaging	-0.74	Pathogenic	0.00	Affected			0.1155	0.4556		-3	-3	2.9	46.09
c.3151G>T	G1051C 2D AIThe SynGAP1 missense variant G1051C is listed in ClinVar as Pathogenic and is not reported in gnomAD. Functional prediction tools show a split assessment: benign calls come from REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. High‑accuracy methods give a benign result from AlphaMissense‑Optimized; the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is tied (2 benign vs. 2 pathogenic) and therefore inconclusive, and Foldetta’s stability prediction is unavailable. Overall, the majority of predictions lean toward a benign effect, which contradicts the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.900141	Binding	0.358	0.936	0.875					Likely Pathogenic		1				-9.050	Likely Pathogenic	0.122	Likely Benign	Likely Benign										0.497	Likely Benign	-0.90	Neutral	0.971	Probably Damaging	0.750	Possibly Damaging	-0.74	Pathogenic	0.10	Tolerated	3.77	5	0.1322	0.4612		-3	-3	2.9	46.09
c.3160G>T	G1054C 2D AIThe SynGAP1 missense variant G1054C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.983019	Disordered	0.878015	Binding	0.389	0.936	0.875											-9.548	Likely Pathogenic	0.118	Likely Benign	Likely Benign										0.297	Likely Benign	-0.59	Neutral	0.999	Probably Damaging	0.907	Possibly Damaging	4.00	Benign	0.10	Tolerated			0.1413	0.4427		-3	-3	2.9	46.09
c.3166G>T	G1056C 2D AIThe SynGAP1 missense variant G1056C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence leans 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.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875											-9.974	Likely Pathogenic	0.122	Likely Benign	Likely Benign										0.432	Likely Benign	-0.70	Neutral	0.994	Probably Damaging	0.777	Possibly Damaging	1.83	Pathogenic	0.06	Tolerated			0.1414	0.4439		-3	-3	2.9	46.09
c.3172G>T	G1058C 2D AIThe SynGAP1 missense variant G1058C is reported in gnomAD (ID 6‑33443724‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and ESM1b. 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.980739	Disordered	0.885724	Binding	0.407	0.929	0.875								6-33443724-G-T	1	6.21e-7	-9.384	Likely Pathogenic	0.132	Likely Benign	Likely Benign										0.264	Likely Benign	-0.19	Neutral	0.600	Possibly Damaging	0.433	Benign	5.19	Benign	0.01	Affected	3.77	5	0.1456	0.4627		-3	-3	2.9	46.09
c.3178G>T	G1060C 2D AIThe SynGAP1 missense variant G1060C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. 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 for G1060C, 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		0.979242	Disordered	0.913048	Binding	0.407	0.928	0.875											-9.630	Likely Pathogenic	0.116	Likely Benign	Likely Benign										0.363	Likely Benign	-0.60	Neutral	0.999	Probably Damaging	0.917	Probably Damaging	2.63	Benign	0.12	Tolerated			0.1340	0.4227		-3	-3	2.9	46.09
c.3181G>T	G1061C 2D AIThe SynGAP1 missense variant G1061C is listed in ClinVar (ID 536997.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443733‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, 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 ESM1b. 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 (six benign vs. four pathogenic predictions) and the two high‑accuracy tools support a benign classification. This conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978672	Disordered	0.926729	Binding	0.394	0.923	0.875					Conflicting		2	6-33443733-G-T	6	3.73e-6	-9.511	Likely Pathogenic	0.119	Likely Benign	Likely Benign										0.409	Likely Benign	-1.46	Neutral	0.938	Possibly Damaging	0.665	Possibly Damaging	3.97	Benign	0.00	Affected	4.32	2	0.1283	0.4227		-3	-3	2.9	46.09
c.3187G>T	G1063C 2D AIThe SynGAP1 missense variant G1063C is not reported 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, AlphaMissense‑Optimized, and the SGM‑Consensus (which itself is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. 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). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.975134	Disordered	0.945784	Binding	0.394	0.913	0.875											-8.315	Likely Pathogenic	0.106	Likely Benign	Likely Benign										0.075	Likely Benign	-1.07	Neutral	0.938	Possibly Damaging	0.477	Possibly Damaging	4.19	Benign	0.01	Affected			0.1440	0.4639		-3	-3	2.9	46.09
c.3211G>T	G1071C 2D AIThe SynGAP1 missense variant G1071C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy predictions—supports a benign classification, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983740	Binding	0.313	0.905	0.875											-5.364	Likely Benign	0.305	Likely Benign	Likely Benign										0.182	Likely Benign	-2.16	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	4.01	Benign	0.00	Affected			0.1323	0.4227		-3	-3	2.9	46.09
c.3298G>T	G1100C 2D AIThe SynGAP1 missense variant G1100C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments reinforce the benign trend: 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, 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		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875											-6.488	Likely Benign	0.150	Likely Benign	Likely Benign										0.174	Likely Benign	-2.25	Neutral	0.999	Probably Damaging	0.950	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.1354	0.4768		-3	-3	2.9	46.09
c.3337G>T	G1113C 2D AIThe SynGAP1 missense variant G1113C is not reported 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, 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. 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		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875											-7.917	In-Between	0.128	Likely Benign	Likely Benign										0.130	Likely Benign	-1.64	Neutral	0.999	Probably Damaging	0.917	Probably Damaging	2.50	Benign	0.06	Tolerated			0.1325	0.4956		-3	-3	2.9	46.09
c.3349G>T	G1117C 2D AIThe SynGAP1 missense variant G1117C is not reported 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 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 not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750											-9.045	Likely Pathogenic	0.112	Likely Benign	Likely Benign										0.359	Likely Benign	-1.30	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.56	Benign	0.03	Affected			0.1347	0.4612		-3	-3	2.9	46.09
c.3358G>T	G1120C 2D AIThe SynGAP1 missense variant G1120C is not reported 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; those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. 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.” No Foldetta stability result is available. Overall, the majority of evidence points to a benign impact for G1120C, 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		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875											-9.324	Likely Pathogenic	0.112	Likely Benign	Likely Benign										0.311	Likely Benign	-1.32	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	3.60	Benign	0.03	Affected			0.1271	0.4227		-3	-3	2.9	46.09
c.3364G>T	G1122C 2D AIThe SynGAP1 missense variant G1122C is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443916‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b 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 high‑confidence tools—supports a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875								6-33443916-G-T			-8.895	Likely Pathogenic	0.110	Likely Benign	Likely Benign										0.375	Likely Benign	-1.30	Neutral	0.975	Probably Damaging	0.733	Possibly Damaging	4.48	Benign	0.08	Tolerated	3.77	5	0.1343	0.4227		-3	-3	2.9	46.09
c.3367G>T	G1123C 2D AIThe SynGAP1 missense variant G1123C is listed in gnomAD (ID 6‑33443919‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy tools—supports a benign classification. This conclusion is not contradicted by ClinVar, which contains no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875								6-33443919-G-T	1	6.64e-7	-9.329	Likely Pathogenic	0.118	Likely Benign	Likely Benign										0.353	Likely Benign	-1.17	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.34	Benign	0.10	Tolerated	3.77	5	0.1348	0.4227		-3	-3	2.9	46.09
c.3376G>T	G1126C 2D AIThe SynGAP1 missense variant G1126C is listed in ClinVar (ID 469157.0) with an “Uncertain” status and is present in gnomAD (6‑33443928‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are SIFT and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.837209	Binding	0.345	0.918	0.875					Uncertain		1	6-33443928-G-T	11	7.35e-6	-9.389	Likely Pathogenic	0.113	Likely Benign	Likely Benign										0.449	Likely Benign	-1.40	Neutral	0.005	Benign	0.005	Benign	4.74	Benign	0.02	Affected	3.77	5	0.1326	0.4427		-3	-3	2.9	46.09
c.358G>T	G120C 2D AIThe SynGAP1 missense variant G120C 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		0.707965	Disordered	0.659993	Binding	0.359	0.887	0.750											-5.979	Likely Benign	0.179	Likely Benign	Likely Benign										0.041	Likely Benign	-0.73	Neutral	0.410	Benign	0.146	Benign	4.20	Benign	0.10	Tolerated			0.1376	0.4225		-3	-3	2.9	46.09
c.3790G>T	G1264C 2D AIThe SynGAP1 missense variant G1264C 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 G1264C, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.429200	Structured	0.762385	Binding	0.897	0.579	0.000											-5.666	Likely Benign	0.280	Likely Benign	Likely Benign										0.122	Likely Benign	-1.03	Neutral	0.997	Probably Damaging	0.870	Possibly Damaging	2.74	Benign	0.09	Tolerated			0.1087	0.3691		-3	-3	2.9	46.09
c.3907G>T	G1303C 2D AIThe SynGAP1 missense variant G1303C 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		0.871313	Disordered	0.886612	Binding	0.429	0.854	0.875											-5.286	Likely Benign	0.257	Likely Benign	Likely Benign										0.377	Likely Benign	-2.49	Neutral	0.997	Probably Damaging	0.961	Probably Damaging	2.76	Benign	0.02	Affected			0.1319	0.3681		-3	-3	2.9	46.09
c.391G>T	G131C 2D AIThe SynGAP1 missense variant G131C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus again indicates Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of tools predict pathogenicity, and this aligns with the SGM Consensus. Therefore, the variant is most likely pathogenic based on the available predictions, and this conclusion is consistent with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-8.288	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign										0.155	Likely Benign	-4.42	Deleterious	0.998	Probably Damaging	0.840	Possibly Damaging	3.88	Benign	0.00	Affected			0.1339	0.4356		-3	-3	2.9	46.09
c.3949G>T	G1317C 2D AIThe SynGAP1 missense variant G1317C is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451823‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the majority of reliable predictions favor a benign impact, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.908098	Disordered	0.971158	Binding	0.385	0.879	0.750								6-33451823-G-T			-5.850	Likely Benign	0.342	Ambiguous	Likely Benign										0.162	Likely Benign	-3.83	Deleterious	0.939	Possibly Damaging	0.570	Possibly Damaging	3.99	Benign	0.00	Affected	3.77	5	0.1345	0.3753		-3	-3	2.9	46.09
c.4003G>T	G1335C 2D AIThe SynGAP1 missense variant G1335C is listed in gnomAD (variant ID 6-33451877‑G‑T) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750								6-33451877-G-T	1	7.91e-7	-6.878	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.01	Pathogenic	0.00	Affected	3.77	5	0.1376	0.4513		-3	-3	2.9	46.09
c.643G>T	G215C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are premPS and FATHMM; those that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta gives an uncertain result and is listed separately. High‑accuracy methods all predict pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the overwhelming agreement among both general and high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000											-12.295	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.39	Destabilizing	0.2	1.76	Ambiguous	2.08	Destabilizing	0.33	Likely Benign	0.869	Likely Pathogenic	-7.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	5.56	Benign	0.00	Affected			0.1274	0.4640		-3	-3	2.9	46.09
c.925G>T	G309C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a deleterious effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score, all of which classify the change as pathogenic or likely pathogenic. Tools with inconclusive results—Rosetta, Foldetta, and premPS—return uncertain outcomes and do not alter the overall assessment. High‑accuracy methods further support a damaging effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta’s stability analysis is inconclusive. Taken together, the evidence strongly favors a pathogenic interpretation, 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 Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125											-14.331	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.60	Destabilizing	0.4	1.09	Ambiguous	1.85	Ambiguous	0.67	Ambiguous	0.656	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1378	0.4574		-3	-3	2.9	46.09
c.1027G>T	V343F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and premPS, whereas pathogenic predictions are made by SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. No evidence from FoldX or Rosetta alone is available. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-10.709	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	1.51	Ambiguous	0.4	1.28	Ambiguous	1.40	Ambiguous	0.23	Likely Benign	0.324	Likely Benign	-3.37	Deleterious	0.976	Probably Damaging	0.759	Possibly Damaging	1.61	Pathogenic	0.01	Affected			0.0915	0.4552		-1	-1	-1.4	48.04
c.103G>T	V35F 2D AIThe SynGAP1 missense variant V35F is not reported 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 for V35F, 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											-4.114	Likely Benign	0.122	Likely Benign	Likely Benign										0.133	Likely Benign	-0.79	Neutral	0.923	Possibly Damaging	0.865	Possibly Damaging	4.14	Benign	0.00	Affected			0.0765	0.3421		-1	-1	-1.4	48.04
c.1270G>T	V424F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V424F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) yield uncertain or unavailable results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-10.947	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.99	Ambiguous	0.3	-0.37	Likely Benign	0.81	Ambiguous	0.55	Ambiguous	0.275	Likely Benign	-3.66	Deleterious	0.995	Probably Damaging	0.775	Possibly Damaging	3.40	Benign	0.01	Affected			0.0816	0.2094		-1	-1	-1.4	48.04
c.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.1321G>T	V441F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V441F missense variant is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a benign interpretation, and the high‑accuracy predictions are split but favor benign. Thus, the variant is most likely benign based on current computational evidence, 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	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-13.519	Likely Pathogenic	0.653	Likely Pathogenic	Likely Benign	-0.26	Likely Benign	0.0	0.32	Likely Benign	0.03	Likely Benign	0.54	Ambiguous	0.355	Likely Benign	-4.22	Deleterious	0.992	Probably Damaging	0.658	Possibly Damaging	3.37	Benign	0.08	Tolerated			0.0670	0.3269		-1	-1	-1.4	48.04
c.1339G>T	V447F 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V447F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain effect on protein folding. Overall, the majority of predictions lean toward pathogenicity, suggesting the variant is most likely pathogenic, a conclusion that does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000					Uncertain		1				-8.673	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	1.40	Ambiguous	0.3	0.61	Ambiguous	1.01	Ambiguous	0.20	Likely Benign	0.206	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.44	Benign	0.03	Affected			0.0551	0.3055		-1	-1	-1.4	48.04
c.1354G>T	V452F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V452F variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect are Rosetta and FATHMM, whereas the remaining tools (REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Based on the preponderance of evidence, the variant is most likely pathogenic, a conclusion that contradicts its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000					Uncertain		1				-14.769	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	9.21	Destabilizing	0.1	0.37	Likely Benign	4.79	Destabilizing	0.61	Ambiguous	0.511	Likely Pathogenic	-4.94	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.29	Benign	0.00	Affected	3.37	34	0.0564	0.3451		-1	-1	-1.4	48.04	249.4	-35.7	0.0	0.0	0.4	0.1							X	Potentially Pathogenic	The iso-propyl side chain of Val452, located in the middle of an α helix (res. Val441-Ser457), packs against hydrophobic residues in the inter-helix space at the intersection of three α helices (e.g., Leu500, His453, Leu465). In the variant simulations, the larger side chain of Phe452 cannot pack against the opposing α helix (res. Leu489-Glu519) as efficiently as valine. Due to space restrictions, the phenol ring adjusts to make room by rotating slightly sideways in the inter-helix space. Besides this small and local shift, no large-scale effects on the protein structure are seen based on the simulations. However, the size difference between the swapped residues could affect the protein folding process.
c.1663G>T	V555F 2D 3DClick to see structure in 3D Viewer AISynGAP1 V555F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence points to a benign 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	0.013265	Structured	0.008218	Uncertain	0.943	0.225	0.000											-10.965	Likely Pathogenic	0.599	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.3	-2.01	Stabilizing	-0.92	Ambiguous	0.16	Likely Benign	0.440	Likely Benign	-2.85	Deleterious	0.011	Benign	0.013	Benign	-1.20	Pathogenic	0.16	Tolerated			0.0727	0.2366		-1	-1	-1.4	48.04
c.1885G>T	V629F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V629F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain and is not counted as evidence. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is pathogenic. No prediction is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions and the absence of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000											-13.484	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.41	Destabilizing	0.5	4.40	Destabilizing	3.91	Destabilizing	0.64	Ambiguous	0.642	Likely Pathogenic	-4.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.07	Benign	0.00	Affected			0.0560	0.2915		-1	-1	-1.4	48.04
c.2509G>T	V837F 2D AIThe SynGAP1 missense variant V837F is not reported 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 data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-5.223	Likely Benign	0.322	Likely Benign	Likely Benign										0.164	Likely Benign	-1.41	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.60	Benign	0.08	Tolerated			0.0749	0.3744		-1	-1	-1.4	48.04
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.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.2731G>T	V911F 2D AIThe SynGAP1 missense variant V911F is not reported 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 V911F, 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		0.685117	Disordered	0.724137	Binding	0.327	0.914	0.375											-4.454	Likely Benign	0.169	Likely Benign	Likely Benign										0.079	Likely Benign	-1.08	Neutral	0.977	Probably Damaging	0.721	Possibly Damaging	2.68	Benign	0.04	Affected			0.0749	0.4380		-1	-1	-1.4	48.04
c.2746G>T	V916F 2D AIThe SynGAP1 missense variant V916F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates 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 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		0.642678	Disordered	0.835395	Binding	0.308	0.879	0.250											-4.011	Likely Benign	0.123	Likely Benign	Likely Benign										0.121	Likely Benign	-1.18	Neutral	0.642	Possibly Damaging	0.265	Benign	2.67	Benign	0.02	Affected			0.0729	0.4593		-1	-1	-1.4	48.04
c.2974G>T	V992F 2D AIThe SynGAP1 missense variant V992F 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, reports a “Likely Benign” classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and there is no conflict with ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.921728	Binding	0.331	0.917	0.750											-3.131	Likely Benign	0.104	Likely Benign	Likely Benign										0.083	Likely Benign	-1.25	Neutral	0.680	Possibly Damaging	0.356	Benign	4.17	Benign	0.04	Affected			0.0832	0.4083		-1	-1	-1.4	48.04
c.3232G>T	V1078F 2D AIThe SynGAP1 missense variant V1078F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic 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; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign effect for V1078F, 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		0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750											-3.768	Likely Benign	0.570	Likely Pathogenic	Likely Benign										0.142	Likely Benign	-0.97	Neutral	0.977	Probably Damaging	0.722	Possibly Damaging	3.87	Benign	0.02	Affected			0.0677	0.4561		-1	-1	-1.4	48.04
c.328G>T	V110F 2D AIThe SynGAP1 missense variant V110F 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, 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, SGM‑Consensus is Likely Benign, and 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		0.622677	Disordered	0.665934	Binding	0.347	0.860	0.750											-4.872	Likely Benign	0.397	Ambiguous	Likely Benign										0.042	Likely Benign	-1.63	Neutral	0.006	Benign	0.003	Benign	4.13	Benign	0.01	Affected			0.0794	0.4027		-1	-1	-1.4	48.04
c.3472G>T	V1158F 2D AIThe SynGAP1 missense variant V1158F is not 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, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is classified as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence indicates that V1158F is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-3.888	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.02	Affected			0.0792	0.3577		-1	-1	-1.4	48.04
c.916G>T	V306F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V306F is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and AlphaMissense‑Optimized, whereas the remaining tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a pathogenic effect. Overall, the majority of evidence supports a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.363090	Structured	0.315026	Uncertain	0.896	0.287	0.125											-9.311	Likely Pathogenic	0.700	Likely Pathogenic	Likely Benign	13.59	Destabilizing	1.4	6.99	Destabilizing	10.29	Destabilizing	0.23	Likely Benign	0.336	Likely Benign	-3.28	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.74	Pathogenic	0.01	Affected			0.0535	0.3318		-1	-1	-1.4	48.04
c.958G>T	V320F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V320F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on benign impact include REVEL, premPS, and SIFT, whereas tools that agree on pathogenic impact include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as inconclusive. Because the majority of available predictions and the SGM‑Consensus favor pathogenicity, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for V320F. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.419626	Uncertain	0.905	0.266	0.125											-9.958	Likely Pathogenic	0.877	Likely Pathogenic	Ambiguous	1.49	Ambiguous	1.4	1.55	Ambiguous	1.52	Ambiguous	0.44	Likely Benign	0.237	Likely Benign	-3.26	Deleterious	0.994	Probably Damaging	0.944	Probably Damaging	1.79	Pathogenic	0.06	Tolerated			0.0473	0.3064		-1	-1	-1.4	48.04
c.1012G>T	D338Y 2D AIThe SynGAP1 D338Y missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a deleterious effect: premPS is the sole predictor labeling it benign, whereas the remaining seven tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—classify it as pathogenic. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the preponderance of evidence indicates that D338Y is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-14.190	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	1.10	Ambiguous	1.3	0.91	Ambiguous	1.01	Ambiguous	0.22	Likely Benign	0.552	Likely Pathogenic	-6.49	Deleterious	0.989	Probably Damaging	0.832	Possibly Damaging	1.66	Pathogenic	0.00	Affected			0.0687	0.5609		-4	-3	2.2	48.09
c.118G>T	D40Y 2D AIThe SynGAP1 D40Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for D40Y, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-4.313	Likely Benign	0.483	Ambiguous	Likely Benign										0.182	Likely Benign	-1.72	Neutral	0.388	Benign	0.328	Benign	3.98	Benign	0.00	Affected			0.1173	0.7918		-4	-3	2.2	48.09
c.1387G>T	D463Y 2D 3DClick to see structure in 3D Viewer AIClinVar reports no entry for this SynGAP1 D463Y variant, and it 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 PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of conventional tools lean toward pathogenicity, while the high‑accuracy Foldetta suggests benign. Thus, the variant is most likely pathogenic based on the prevailing 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	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-14.387	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.14	Likely Benign	0.1	0.77	Ambiguous	0.32	Likely Benign	0.07	Likely Benign	0.399	Likely Benign	-7.95	Deleterious	0.998	Probably Damaging	0.904	Possibly Damaging	3.35	Benign	0.14	Tolerated			0.0540	0.6213		-4	-3	2.2	48.09
c.1399G>T	D467Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D467Y is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Foldetta, premPS, and SIFT, whereas pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No evidence from Rosetta is available due to its uncertain status. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and this does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-14.373	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.36	Likely Benign	0.1	-0.60	Ambiguous	-0.12	Likely Benign	0.07	Likely Benign	0.846	Likely Pathogenic	-8.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.28	Pathogenic	0.07	Tolerated			0.0517	0.5521		-4	-3	2.2	48.09
c.1420G>T	D474Y 2D AIThe SynGAP1 missense variant D474Y is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include FoldX, Foldetta, and premPS, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the preponderance of evidence points to a pathogenic effect for D474Y. This conclusion does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-14.647	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.5	-0.74	Ambiguous	-0.24	Likely Benign	0.20	Likely Benign	0.864	Likely Pathogenic	-7.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.30	Pathogenic	0.01	Affected			0.0493	0.4237		-4	-3	2.2	48.09
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.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.1747G>T	D583Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D583Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect are Foldetta and premPS, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-12.187	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.2	-1.10	Ambiguous	-0.18	Likely Benign	0.10	Likely Benign	0.760	Likely Pathogenic	-8.50	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.45	Pathogenic	0.01	Affected			0.0537	0.3868		-4	-3	2.2	48.09
c.1756G>T	D586Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include FoldX, SIFT, and premPS, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. Rosetta and Foldetta, which assess protein‑folding stability, return uncertain results and are therefore not considered evidence for either direction. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as pathogenic, and Foldetta as uncertain. Overall, the preponderance of pathogenic predictions (13 vs. 3 benign) suggests that D586Y is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-12.916	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.4	1.09	Ambiguous	0.73	Ambiguous	-0.49	Likely Benign	0.712	Likely Pathogenic	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.16	Pathogenic	0.41	Tolerated			0.0623	0.5634		-4	-3	2.2	48.09
c.178G>T	D60Y 2D AIThe SynGAP1 D60Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the D60Y variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-7.748	In-Between	0.971	Likely Pathogenic	Likely Pathogenic										0.221	Likely Benign	-2.60	Deleterious	0.972	Probably Damaging	0.969	Probably Damaging	3.90	Benign	0.00	Affected			0.0517	0.7790		-4	-3	2.2	48.09
c.1846G>T	D616Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D616Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX or Rosetta alone is conclusive. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-12.638	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	0.3	1.32	Ambiguous	1.51	Ambiguous	0.35	Likely Benign	0.374	Likely Benign	-7.43	Deleterious	0.999	Probably Damaging	0.970	Probably Damaging	3.28	Benign	0.01	Affected			0.0465	0.4069		-4	-3	2.2	48.09
c.184G>T	D62Y 2D AIThe SynGAP1 missense variant D62Y is not reported in ClinVar (no ClinVar ID) 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. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125											-6.313	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-2.17	Neutral	0.388	Benign	0.328	Benign	4.03	Benign	0.00	Affected			0.0657	0.5588		-4	-3	2.2	48.09
c.1930G>T	D644Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 D644Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. The remaining tools, FoldX, REVEL, premPS, polyPhen‑2 HumVar, and FATHMM, support a benign effect, while PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default support a pathogenic effect. Overall, the majority of evidence leans toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-10.143	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.1	-1.18	Ambiguous	-0.58	Ambiguous	-0.04	Likely Benign	0.318	Likely Benign	-4.93	Deleterious	0.968	Probably Damaging	0.311	Benign	3.44	Benign	0.02	Affected			0.0679	0.6094		-4	-3	2.2	48.09
c.2011G>T	D671Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized and the SGM‑Consensus both indicate pathogenicity, while Foldetta predicts a benign effect on protein stability. Because the majority of standard predictors lean toward pathogenicity and the two high‑confidence tools also favor a deleterious outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-13.107	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.05	Likely Benign	0.18	Likely Benign	0.11	Likely Benign	0.385	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.961	Probably Damaging	3.29	Benign	0.00	Affected			0.0564	0.6376		-4	-3	2.2	48.09
c.2050G>T	D684Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684Y 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: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. Only premPS and FATHMM predict a benign effect. 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 outputs) is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the absence of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-15.224	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	1.5	2.12	Destabilizing	2.89	Destabilizing	-0.06	Likely Benign	0.600	Likely Pathogenic	-8.98	Deleterious	1.000	Probably Damaging	0.963	Probably Damaging	3.44	Benign	0.00	Affected			0.0575	0.6564		-4	-3	2.2	48.09
c.211G>T	D71Y 2D AIThe SynGAP1 missense variant D71Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375											-4.090	Likely Benign	0.740	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.49	Neutral	0.842	Possibly Damaging	0.189	Benign	4.00	Benign	0.00	Affected			0.0584	0.6086		-4	-3	2.2	48.09
c.2158G>T	D720Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, while pathogenic predictions are made by SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. The high‑accuracy consensus (SGM Consensus) classifies the variant as Likely Pathogenic, and Foldetta likewise yields an uncertain stability change. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-14.771	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	-0.74	Ambiguous	0.1	-1.38	Ambiguous	-1.06	Ambiguous	0.20	Likely Benign	0.499	Likely Benign	-7.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.0626	0.5973		-4	-3	2.2	48.09
c.2284G>T	D762Y 2D AIThe SynGAP1 D762Y variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a larger group predicts a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; Foldetta (a protein‑folding stability approach combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-6.959	Likely Benign	0.905	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-3.24	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.07	Pathogenic	0.01	Affected			0.0700	0.7929		-4	-3	2.2	48.09
c.2302G>T	D768Y 2D AIThe SynGAP1 missense variant D768Y is listed in ClinVar with status “Uncertain” (ClinVar ID 1061652.0) and is present in gnomAD (variant ID 6‑33442460‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar designation of uncertainty. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250					Uncertain		1	6-33442460-G-T			-9.866	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous										0.234	Likely Benign	-2.86	Deleterious	0.989	Probably Damaging	0.806	Possibly Damaging	4.01	Benign	0.07	Tolerated	3.64	6	0.0581	0.7525		-4	-3	2.2	48.09
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.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.2476G>T	D826Y 2D AIThe SynGAP1 missense variant D826Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect for D826Y. Thus, the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-8.029	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.336	Likely Benign	-4.25	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.47	Pathogenic	0.00	Affected			0.0683	0.7410		-4	-3	2.2	48.09
c.2533G>T	D845Y 2D AIThe SynGAP1 missense variant D845Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that D845Y is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-9.917	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.384	Likely Benign	-6.55	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0590	0.6699		-4	-3	2.2	48.09
c.2545G>T	D849Y 2D AIThe SynGAP1 missense variant D849Y has no ClinVar entry and is not reported in gnomAD. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy tools 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 majority of reliable predictors and consensus analyses indicate a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with existing clinical evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500											-6.200	Likely Benign	0.383	Ambiguous	Likely Benign										0.150	Likely Benign	-1.92	Neutral	0.971	Probably Damaging	0.773	Possibly Damaging	4.13	Benign	0.00	Affected			0.0767	0.7690		-4	-3	2.2	48.09
c.2602G>T	D868Y 2D AIThe SynGAP1 missense variant D868Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate deleteriousness. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for D868Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-6.031	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.256	Likely Benign	-2.90	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.47	Pathogenic	0.05	Affected			0.1115	0.6847		-4	-3	2.2	48.09
c.2740G>T	D914Y 2D AIThe SynGAP1 missense variant D914Y is not 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; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) and the lack of a benign consensus from the high‑accuracy methods suggest that D914Y is most likely pathogenic. This prediction does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250											-4.768	Likely Benign	0.740	Likely Pathogenic	Likely Benign										0.239	Likely Benign	-2.65	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	2.62	Benign	0.01	Affected			0.0907	0.7583		-4	-3	2.2	48.09
c.2809G>T	D937Y 2D AIThe SynGAP1 missense variant D937Y is not 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 due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic based on current computational evidence, 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.			0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625											-4.720	Likely Benign	0.711	Likely Pathogenic	Likely Benign										0.137	Likely Benign	-2.52	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.67	Benign	0.05	Affected			0.1305	0.7494		-4	-3	2.2	48.09
c.2920G>T	D974Y 2D AIThe SynGAP1 missense variant D974Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of computational evidence points to a benign impact, which is consistent with the absence of ClinVar pathogenic classification and gnomAD observations. Thus, the variant is most likely benign, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625											-4.290	Likely Benign	0.384	Ambiguous	Likely Benign										0.130	Likely Benign	-1.85	Neutral	0.716	Possibly Damaging	0.284	Benign	4.13	Benign	0.01	Affected			0.1072	0.6627		-4	-3	2.2	48.09
c.2959G>T	D987Y 2D AIThe SynGAP1 missense variant D987Y is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. 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. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as likely pathogenic (3 pathogenic vs 1 benign). AlphaMissense‑Optimized returns an uncertain result, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-6.208	Likely Benign	0.831	Likely Pathogenic	Ambiguous										0.274	Likely Benign	-4.41	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.0632	0.6818		-4	-3	2.2	48.09
c.3022G>T	D1008Y 2D AIThe SynGAP1 missense variant D1008Y is not 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 results are not provided. Overall, the balance of evidence favors a pathogenic classification, 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.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-5.371	Likely Benign	0.928	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-3.71	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.62	Benign	0.00	Affected			0.1043	0.6293		-4	-3	2.2	48.09
c.3046G>T	D1016Y 2D AIThe SynGAP1 missense variant D1016Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also 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 variant. High‑accuracy assessment therefore points to a Likely Pathogenic classification from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Based on the preponderance of pathogenic predictions and the lack of contradictory evidence from ClinVar, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-4.432	Likely Benign	0.832	Likely Pathogenic	Ambiguous										0.350	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.947	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.1111	0.6531		-4	-3	2.2	48.09
c.3076G>T	D1026Y 2D AIThe SynGAP1 missense variant D1026Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-6.999	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.200	Likely Benign	-3.08	Deleterious	0.938	Possibly Damaging	0.596	Possibly Damaging	2.47	Pathogenic	0.00	Affected			0.0676	0.4936		-4	-3	2.2	48.09
c.3499G>T	D1167Y 2D AIThe SynGAP1 missense variant D1167Y is not 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, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a 2‑to‑2 split and is therefore inconclusive. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six pathogenic vs. three benign) indicate that D1167Y is most likely pathogenic. This assessment 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.			0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-4.050	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.281	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.995	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.0640	0.7307		-4	-3	2.2	48.09
c.3562G>T	D1188Y 2D AIThe SynGAP1 D1188Y 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 predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evaluated tools (seven pathogenic versus three benign) indicate a pathogenic impact. This prediction aligns with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-6.482	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.490	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	5.40	Benign	0.00	Affected			0.0450	0.4714		-4	-3	2.2	48.09
c.3577G>T	D1193Y 2D AIThe SynGAP1 missense variant D1193Y 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 (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375											-8.233	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous										0.484	Likely Benign	-2.94	Deleterious	0.992	Probably Damaging	0.947	Probably Damaging	5.50	Benign	0.00	Affected			0.0477	0.4111		-4	-3	2.2	48.09
c.3766G>T	D1256Y 2D AIThe SynGAP1 missense variant D1256Y is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a deleterious effect. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that D1256Y is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-15.855	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.507	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.0446	0.4275		-4	-3	2.2	48.09
c.3826G>T	D1276Y 2D AIThe SynGAP1 missense variant D1276Y is catalogued in gnomAD (ID 6‑33447874‑G‑T) but has no ClinVar entry. Functional prediction tools fall into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic effect; Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status, as none is currently reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625								6-33447874-G-T			-1.558	Likely Benign	0.768	Likely Pathogenic	Likely Benign										0.325	Likely Benign	-6.66	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	1.18	Pathogenic	0.00	Affected	3.77	5	0.0385	0.5082		-3	-4	2.2	48.09
c.3877G>T	D1293Y 2D AIThe SynGAP1 missense variant D1293Y is not 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 predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic classification, with no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.892346	Binding	0.569	0.801	0.625											-5.452	Likely Benign	0.392	Ambiguous	Likely Benign										0.310	Likely Benign	-6.15	Deleterious	0.995	Probably Damaging	0.897	Possibly Damaging	2.15	Pathogenic	0.00	Affected			0.0627	0.3577		-4	-3	2.2	48.09
c.4024G>T	D1342Y 2D AIThe SynGAP1 missense variant D1342Y is reported in gnomAD (6‑33451898‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.981682	Binding	0.316	0.678	0.875								6-33451898-G-T			-4.108	Likely Benign	0.398	Ambiguous	Likely Benign										0.095	Likely Benign	-1.34	Neutral	0.939	Possibly Damaging	0.496	Possibly Damaging	3.98	Benign	0.01	Affected	4.32	4	0.0868	0.5377		-3	-4	2.2	48.09
c.451G>T	D151Y 2D AIThe SynGAP1 D151Y variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the D151Y 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		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-13.174	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.340	Likely Benign	-5.16	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	3.85	Benign	0.00	Affected			0.0567	0.7560		-4	-3	2.2	48.09
c.499G>T	D167Y 2D AIThe SynGAP1 missense variant D167Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas the remaining eight predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized—and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact for D167Y, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-14.228	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.414	Likely Benign	-4.23	Deleterious	0.898	Possibly Damaging	0.557	Possibly Damaging	3.90	Benign	0.00	Affected			0.0493	0.6358		-4	-3	2.2	48.09
c.505G>T	D169Y 2D AIThe SynGAP1 missense variant D169Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability data are available. Based on the overall pattern of predictions, the variant is most likely pathogenic, 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 Pathogenic		0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-13.524	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous										0.282	Likely Benign	-3.71	Deleterious	0.651	Possibly Damaging	0.347	Benign	4.01	Benign	0.00	Affected			0.0571	0.6896		-4	-3	2.2	48.09
c.601G>T	D201Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D201Y missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, and FATHMM. Those that predict a pathogenic effect comprise SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Rosetta. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus predicts likely pathogenic; Foldetta is uncertain. Because the majority of consensus and individual predictors (seven pathogenic vs four benign) lean toward a damaging outcome, the variant is most likely pathogenic. This assessment is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428570	Uncertain	0.698	0.447	0.125											-10.916	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.2	2.39	Destabilizing	1.34	Ambiguous	0.31	Likely Benign	0.334	Likely Benign	-4.93	Deleterious	1.000	Probably Damaging	0.960	Probably Damaging	4.02	Benign	0.02	Affected			0.0431	0.5371		-4	-3	2.2	48.09
c.607G>T	D203Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203Y missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or folding result is missing or inconclusive. Overall, the majority of individual tools lean toward benign, and two of the three high‑accuracy methods also predict benign, so the variant is most likely benign. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-11.651	Likely Pathogenic	0.597	Likely Pathogenic	Likely Benign	-0.36	Likely Benign	0.0	0.09	Likely Benign	-0.14	Likely Benign	0.05	Likely Benign	0.260	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	3.96	Benign	0.01	Affected			0.0382	0.4436		-4	-3	2.2	48.09
c.67G>T	D23Y 2D AIThe SynGAP1 D23Y missense variant is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33420331‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive 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 is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375								6-33420331-G-T			-4.191	Likely Benign	0.729	Likely Pathogenic	Likely Benign										0.142	Likely Benign	-2.87	Deleterious	0.972	Probably Damaging	0.861	Possibly Damaging	3.46	Benign	0.00	Affected	4.32	1	0.1013	0.7951		-3	-4	2.2	48.09
c.718G>T	D240Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D240Y missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, premPS, and FATHMM; pathogenic predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Taken together, the overwhelming majority of reliable predictors indicate a pathogenic effect for D240Y. This conclusion is consistent with the lack 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 Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000											-16.890	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.3	1.07	Ambiguous	0.68	Ambiguous	-0.01	Likely Benign	0.899	Likely Pathogenic	-7.90	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	5.77	Benign	0.00	Affected			0.0439	0.4932		-4	-3	2.2	48.09
c.763G>T	D255Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore not used as evidence. 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 conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-13.180	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.25	Ambiguous	0.2	0.96	Ambiguous	1.11	Ambiguous	0.13	Likely Benign	0.832	Likely Pathogenic	-7.77	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.73	Benign	0.00	Affected			0.0464	0.5178		-4	-3	2.2	48.09
c.781G>T	D261Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D261Y missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are premPS and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No prediction or folding stability result is missing or inconclusive beyond the stated uncertainties. Overall, the preponderance of evidence points to a pathogenic effect for D261Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-14.961	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous	2.93	Destabilizing	2.1	0.81	Ambiguous	1.87	Ambiguous	-0.12	Likely Benign	0.886	Likely Pathogenic	-5.50	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.73	Benign	0.01	Affected			0.0474	0.5476		-4	-3	2.2	48.09
c.859G>T	D287Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D287Y missense variant is reported in ClinVar as Pathogenic (ClinVar ID 2263930.0) and is not found in gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, and premPS, whereas pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. High‑accuracy assessments give a pathogenic verdict from AlphaMissense‑Optimized, a Likely Pathogenic consensus from SGM, and a benign outcome from Foldetta. Overall, the majority of evidence points to a deleterious effect. Therefore, the variant is most likely pathogenic, in agreement with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000					Likely Pathogenic		1				-12.877	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.21	Likely Benign	0.2	0.48	Likely Benign	0.35	Likely Benign	0.27	Likely Benign	0.663	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.51	Pathogenic	0.00	Affected	3.38	23	0.0597	0.7361		-4	-3	2.2	48.09	257.8	-44.4	-0.6	1.6	0.2	0.3	X	X						Potentially Pathogenic	The carboxylate group of Asp287, located at the beginning of a β hairpin loop linking two anti-parallel β sheet strands (res. Arg279-Leu286, res. Met289-Pro298), maintains a salt bridge with the guanidinium group of Arg324 in the β sheet during the WT simulations. In the variant simulations, the phenol group of the Tyr287 side chain is unable to form a salt bridge with the guanidinium group of Arg324, which could weaken the tertiary structure assembly of the C2 domain. However, the phenol group of Tyr287 frequently stacks with the Arg324 guanidinium side chain, which could help maintain the tertiary structure, especially compared to the D287H variant. The destabilization of the C2 domain could adversely affect the stability of the SynGAP-membrane association.
c.862G>T	D288Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, and premPS; pathogenic predictions from SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from the available tools suggests a benign effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-15.269	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.11	Likely Benign	0.2	1.10	Ambiguous	0.61	Ambiguous	0.10	Likely Benign	0.472	Likely Benign	-7.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.0635	0.5009		-4	-3	2.2	48.09
c.910G>T	D304Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also labeled 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 the majority of evidence pointing toward pathogenicity, the variant is most likely pathogenic; this assessment does not conflict with ClinVar, which contains no entry for D304Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-10.495	Likely Pathogenic	0.845	Likely Pathogenic	Ambiguous	0.60	Ambiguous	0.2	0.14	Likely Benign	0.37	Likely Benign	0.37	Likely Benign	0.468	Likely Benign	-6.29	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.76	Pathogenic	0.00	Affected			0.0623	0.6566		-4	-3	2.2	48.09
c.988G>T	D330Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D330Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and premPS, whereas the remaining tools—including SGM‑Consensus, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; FoldX is uncertain and therefore not counted. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates that D330Y is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-14.200	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.98	Ambiguous	0.6	2.90	Destabilizing	2.44	Destabilizing	0.35	Likely Benign	0.472	Likely Benign	-6.47	Deleterious	0.998	Probably Damaging	0.948	Probably Damaging	0.89	Pathogenic	0.00	Affected			0.0539	0.4689		-4	-3	2.2	48.09
c.994G>T	D332Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D332Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and premPS, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a likely pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, the majority of evidence points to a pathogenic impact for D332Y, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-14.210	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.6	-0.07	Likely Benign	0.54	Ambiguous	0.41	Likely Benign	0.485	Likely Benign	-7.33	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.20	Pathogenic	0.00	Affected			0.0372	0.4018		-4	-3	2.2	48.09
c.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.1318A>T	N440Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, AlphaMissense‑Default, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yielding an uncertain stability change. Overall, the majority of predictions lean toward a benign interpretation, and this is consistent with the lack of ClinVar annotation. Therefore, 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 Pathogenic	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-10.586	Likely Pathogenic	0.674	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	1.25	Ambiguous	1.03	Ambiguous	0.20	Likely Benign	0.135	Likely Benign	-3.81	Deleterious	0.931	Possibly Damaging	0.230	Benign	3.43	Benign	0.07	Tolerated			0.0535	0.3624		-2	-2	2.2	49.07
c.133A>T	N45Y 2D AIThe SynGAP1 missense variant N45Y is not reported 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. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign 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		0.401658	Structured	0.431853	Uncertain	0.498	0.741	0.375											-5.773	Likely Benign	0.502	Ambiguous	Likely Benign										0.180	Likely Benign	-1.18	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.04	Benign	0.00	Affected			0.0741	0.7255		-2	-2	2.2	49.07
c.1459A>T	N487Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487Y has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM, whereas the majority of algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for N487Y, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-14.921	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.0	-0.05	Likely Benign	0.55	Ambiguous	0.33	Likely Benign	0.652	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.00	Affected			0.0587	0.2946		-2	-2	2.2	49.07
c.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.160A>T	N54Y 2D AIThe SynGAP1 missense variant N54Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). High‑accuracy methods show AlphaMissense‑Optimized as benign; the SGM Consensus is unavailable, and Foldetta results are not provided, so its stability prediction is also unavailable. Overall, more tools (five) predict pathogenicity than benign (four), and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. Thus, the variant is most likely pathogenic based on current computational predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000											-9.313	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.57	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.16	Benign	0.00	Affected			0.0512	0.6687		-2	-2	2.2	49.07
c.1624A>T	N542Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542Y 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 majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts likely pathogenic; Foldetta, a protein‑folding stability approach combining FoldX‑MD and Rosetta, remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for the variant, 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	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-14.488	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	-0.66	Ambiguous	0.0	-0.56	Ambiguous	-0.61	Ambiguous	0.42	Likely Benign	0.872	Likely Pathogenic	-6.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.46	Pathogenic	0.02	Affected			0.0578	0.5480		-2	-2	2.2	49.07
c.1666A>T	N556Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic impact are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus as pathogenic. Taken together, the majority of evidence (8 pathogenic vs 5 benign) points to a pathogenic effect, 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	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-12.533	Likely Pathogenic	0.730	Likely Pathogenic	Likely Benign	-0.01	Likely Benign	0.1	-0.40	Likely Benign	-0.21	Likely Benign	0.28	Likely Benign	0.743	Likely Pathogenic	-6.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.40	Pathogenic	0.01	Affected			0.0690	0.3157		-2	-2	2.2	49.07
c.1894A>T	N632Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N632Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX and premPS, while pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further indicate that AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this 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	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000											-15.245	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.7	-1.02	Ambiguous	-0.54	Ambiguous	0.28	Likely Benign	0.844	Likely Pathogenic	-7.04	Deleterious	0.999	Probably Damaging	0.960	Probably Damaging	-1.55	Pathogenic	0.00	Affected			0.0698	0.5959		-2	-2	2.2	49.07
c.1903A>T	N635Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N635Y has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include Foldetta, premPS, FATHMM, AlphaMissense‑Optimized, and Rosetta. Those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX is uncertain and therefore treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating likely pathogenic, and Foldetta predicting a benign outcome. Overall, the majority of tools lean toward a benign interpretation, 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	0.039760	Structured	0.060246	Uncertain	0.900	0.252	0.000											-14.931	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign	0.73	Ambiguous	0.3	-0.11	Likely Benign	0.31	Likely Benign	-0.16	Likely Benign	0.554	Likely Pathogenic	-7.64	Deleterious	0.998	Probably Damaging	0.922	Probably Damaging	2.88	Benign	0.00	Affected			0.0750	0.3632		-2	-2	2.2	49.07
c.1948A>T	N650Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta remains uncertain. Overall, the evidence strongly favors a pathogenic classification for the variant, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this mutation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000											-16.923	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.3	1.32	Ambiguous	1.44	Ambiguous	0.16	Likely Benign	0.587	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.984	Probably Damaging	3.03	Benign	0.03	Affected			0.0852	0.3865		-2	-2	2.2	49.07
c.2005A>T	N669Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, and premPS. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. 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. With eight pathogenic predictions versus three benign, the overall evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-13.548	Likely Pathogenic	0.802	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.4	1.29	Ambiguous	0.87	Ambiguous	0.21	Likely Benign	0.546	Likely Pathogenic	-7.01	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.34	Benign	0.00	Affected			0.0666	0.4151		-2	-2	2.2	49.07
c.2023A>T	N675Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675Y is not 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-9.981	Likely Pathogenic	0.553	Ambiguous	Likely Benign	3.02	Destabilizing	1.3	-0.81	Ambiguous	1.11	Ambiguous	0.19	Likely Benign	0.439	Likely Benign	-5.86	Deleterious	1.000	Probably Damaging	0.955	Probably Damaging	3.38	Benign	0.01	Affected			0.0603	0.6417		-2	-2	2.2	49.07
c.2155A>T	N719Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also uncertain. Overall, the majority of evaluated tools (7 benign vs 4 pathogenic) support a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-11.005	Likely Pathogenic	0.302	Likely Benign	Likely Benign	-0.38	Likely Benign	0.0	-0.62	Ambiguous	-0.50	Ambiguous	0.33	Likely Benign	0.187	Likely Benign	-4.15	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.09	Tolerated			0.0412	0.3951		-2	-2	2.2	49.07
c.2179A>T	N727Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727Y has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Two tools remain inconclusive: AlphaMissense‑Default and Rosetta. Separately, the high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of individual predictors and the SGM Consensus lean toward a pathogenic interpretation, while the high‑accuracy folding‑stability assessment is benign. Thus, the variant is most likely pathogenic based on the available predictions, 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		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.106	Likely Pathogenic	0.426	Ambiguous	Likely Benign	-0.12	Likely Benign	0.1	-0.52	Ambiguous	-0.32	Likely Benign	0.35	Likely Benign	0.347	Likely Benign	-5.34	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.12	Pathogenic	0.02	Affected			0.0563	0.6091		-2	-2	2.2	49.07
c.2185A>T	N729Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta remains uncertain. The high‑accuracy consensus methods give a consistent benign signal: 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. Taken together, the overwhelming majority of evidence points to a benign effect. Thus, 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		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625											-2.284	Likely Benign	0.216	Likely Benign	Likely Benign	0.00	Likely Benign	0.1	0.82	Ambiguous	0.41	Likely Benign	0.08	Likely Benign	0.060	Likely Benign	-2.35	Neutral	0.575	Possibly Damaging	0.053	Benign	3.27	Benign	0.14	Tolerated			0.0570	0.4073		-2	-2	2.2	49.07
c.2290A>T	N764Y 2D AIThe SynGAP1 missense variant N764Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta data are unavailable. Overall, the balance of evidence favors a pathogenic interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.380708	Structured	0.919527	Binding	0.305	0.861	0.250											-5.914	Likely Benign	0.680	Likely Pathogenic	Likely Benign										0.158	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.967	Probably Damaging	2.58	Benign	0.01	Affected			0.0552	0.4175		-2	-2	2.2	49.07
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.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.2512A>T	N838Y 2D AIThe SynGAP1 missense variant N838Y 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 majority of predictions (six pathogenic versus three benign) and the SGM‑Consensus lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-9.020	Likely Pathogenic	0.722	Likely Pathogenic	Likely Benign										0.266	Likely Benign	-4.09	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.05	Affected			0.0621	0.4258		-2	-2	2.2	49.07
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.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.2785A>T	N929Y 2D AIThe SynGAP1 missense variant N929Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL predicts benign, whereas the remaining eleven predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.327	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.391	Likely Benign	-6.02	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.0656	0.6489		-2	-2	2.2	49.07
c.3079A>T	N1027Y 2D AIThe SynGAP1 missense variant N1027Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500											-5.799	Likely Benign	0.626	Likely Pathogenic	Likely Benign										0.074	Likely Benign	-2.15	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.70	Benign	0.03	Affected			0.0611	0.6133		-2	-2	2.2	49.07
c.3268A>T	N1090Y 2D AIThe SynGAP1 missense variant N1090Y is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support a benign outcome: 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 points to a benign effect for the variant, 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		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000											-4.744	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-2.26	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.05	Affected			0.0661	0.5998		-2	-2	2.2	49.07
c.3433A>T	N1145Y 2D AIThe SynGAP1 missense variant N1145Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign, while Foldetta results are unavailable. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus leans benign. 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.			0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000											-2.945	Likely Benign	0.451	Ambiguous	Likely Benign										0.543	Likely Pathogenic	-4.07	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.40	Benign	0.01	Affected			0.0622	0.6337		-2	-2	2.2	49.07
c.3478A>T	N1160Y 2D AIThe SynGAP1 missense variant N1160Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.074	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.421	Likely Benign	-4.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0591	0.5681		-2	-2	2.2	49.07
c.3637A>T	N1213Y 2D AIThe SynGAP1 missense variant N1213Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. 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 predicts benign, while high‑accuracy folding‑stability predictions from Foldetta are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and the consensus and high‑accuracy methods lean toward 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.		Coiled-coil	0.580690	Disordered	0.521638	Binding	0.888	0.561	0.500											-8.972	Likely Pathogenic	0.483	Ambiguous	Likely Benign										0.083	Likely Benign	-2.67	Deleterious	0.920	Possibly Damaging	0.657	Possibly Damaging	2.68	Benign	0.02	Affected			0.0439	0.3681		-2	-2	2.2	49.07
c.3916A>T	N1306Y 2D AIThe SynGAP1 missense variant N1306Y is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance 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		0.795062	Disordered	0.902190	Binding	0.367	0.888	0.875											-4.193	Likely Benign	0.298	Likely Benign	Likely Benign										0.273	Likely Benign	-5.59	Deleterious	0.961	Probably Damaging	0.825	Possibly Damaging	2.54	Benign	0.00	Affected			0.0732	0.6658		-2	-2	2.2	49.07
c.3946A>T	N1316Y 2D AIThe SynGAP1 missense variant N1316Y is reported in gnomAD (variant ID 6‑33451820‑A‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, polyPhen2_HumVar, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen2_HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is available). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750								6-33451820-A-T			-5.579	Likely Benign	0.392	Ambiguous	Likely Benign										0.101	Likely Benign	-2.48	Neutral	0.939	Possibly Damaging	0.396	Benign	3.90	Benign	0.00	Affected	3.77	5	0.0671	0.5365		-2	-2	2.2	49.07
c.4000A>T	N1334Y 2D AIThe SynGAP1 missense variant N1334Y is not 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, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive; Foldetta results are unavailable. Overall, the majority of conventional tools predict a pathogenic impact, but the single high‑accuracy benign prediction and the inconclusive consensus suggest uncertainty. Consequently, the variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict any ClinVar annotation because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.916	Likely Benign	0.770	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-4.62	Deleterious	0.985	Probably Damaging	0.852	Possibly Damaging	3.49	Benign	0.00	Affected			0.0716	0.5447		-2	-2	2.2	49.07
c.4015A>T	N1339Y 2D AIThe SynGAP1 missense variant N1339Y is not 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) and Foldetta data are unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the variant’s impact uncertain. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.771762	Disordered	0.977585	Binding	0.396	0.687	1.000											-3.808	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.319	Likely Benign	-4.83	Deleterious	0.994	Probably Damaging	0.990	Probably Damaging	2.87	Benign	0.00	Affected			0.0697	0.6573		-2	-2	2.2	49.07
c.595A>T	N199Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N199Y 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, Foldetta, premPS, polyPhen‑2 (HumVar), FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from SIFT, PROVEAN, polyPhen‑2 (HumDiv), and ESM1b. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates benign stability. Overall, the majority of conventional tools (8 benign vs. 4 pathogenic) favor a benign effect, and this interpretation does not conflict with the absence of ClinVar annotation. Therefore, the variant is most likely benign based on the current predictive evidence, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.390993	Structured	0.431347	Uncertain	0.571	0.473	0.125											-8.575	Likely Pathogenic	0.391	Ambiguous	Likely Benign	-0.06	Likely Benign	0.1	0.14	Likely Benign	0.04	Likely Benign	0.20	Likely Benign	0.097	Likely Benign	-3.12	Deleterious	0.952	Possibly Damaging	0.395	Benign	4.15	Benign	0.04	Affected			0.0389	0.5630		-2	-2	2.2	49.07
c.733A>T	N245Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N245Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, and FATHMM, whereas pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority (3/4). AlphaMissense‑Optimized independently predicts pathogenicity, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. premPS remains uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Thus, the variant is most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.454136	Structured	0.315864	Uncertain	0.831	0.351	0.000											-12.476	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	-0.36	Likely Benign	0.1	0.11	Likely Benign	-0.13	Likely Benign	0.59	Ambiguous	0.855	Likely Pathogenic	-6.68	Deleterious	0.995	Probably Damaging	0.880	Possibly Damaging	5.86	Benign	0.00	Affected			0.0706	0.6771		-2	-2	2.2	49.07
c.757A>T	N253Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, FATHMM, and premPS, whereas a larger set—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Because the majority of evidence points to a deleterious impact, the variant is most likely pathogenic; this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-14.749	Likely Pathogenic	0.920	Likely Pathogenic	Ambiguous	0.27	Likely Benign	0.1	1.13	Ambiguous	0.70	Ambiguous	0.29	Likely Benign	0.896	Likely Pathogenic	-7.01	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	5.55	Benign	0.01	Affected			0.0642	0.7055		-2	-2	2.2	49.07
c.766A>T	N256Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, and FATHMM, whereas the majority of tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label it pathogenic. The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the preponderance of evidence from standard predictors and the two high‑accuracy pathogenic calls suggests 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	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250											-10.881	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.2	-0.80	Ambiguous	-0.32	Likely Benign	0.30	Likely Benign	0.868	Likely Pathogenic	-6.85	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.83	Benign	0.00	Affected			0.0493	0.5881		-2	-2	2.2	49.07
c.784A>T	N262Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N262Y is 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, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, 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 uncertain. Overall, the majority of predictions (seven pathogenic vs. three benign) lean toward a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.284882	Structured	0.399879	Uncertain	0.912	0.240	0.000											-12.177	Likely Pathogenic	0.490	Ambiguous	Likely Benign	1.86	Ambiguous	0.5	0.52	Ambiguous	1.19	Ambiguous	0.36	Likely Benign	0.858	Likely Pathogenic	-6.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.85	Benign	0.01	Affected			0.0445	0.3877		-2	-2	2.2	49.07
c.943A>T	N315Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315Y is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. The high‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence slightly favors a pathogenic interpretation, with six pathogenic‑predicted tools versus five benign‑predicted tools, and the high‑accuracy consensus leaning pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-8.303	Likely Pathogenic	0.339	Likely Benign	Likely Benign	-1.03	Ambiguous	0.5	-0.85	Ambiguous	-0.94	Ambiguous	-0.10	Likely Benign	0.420	Likely Benign	-3.81	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.93	Pathogenic	1.00	Tolerated			0.0613	0.6732		-2	-2	2.2	49.07
c.946A>T	N316Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316Y 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, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign impact. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-11.226	Likely Pathogenic	0.767	Likely Pathogenic	Likely Benign	0.53	Ambiguous	0.5	-0.09	Likely Benign	0.22	Likely Benign	0.50	Likely Benign	0.454	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.81	Pathogenic	0.01	Affected			0.0574	0.6971		-2	-2	2.2	49.07
c.1189T>C	C397R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, and AlphaMissense‑Default. The remaining tools (FoldX, premPS, ESM1b) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (2 benign vs. 1 pathogenic, 1 uncertain), and Foldetta predicts a benign impact on protein folding stability. 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.		C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250											-7.094	In-Between	0.708	Likely Pathogenic	Likely Benign	0.55	Ambiguous	0.8	0.40	Likely Benign	0.48	Likely Benign	0.96	Ambiguous	0.514	Likely Pathogenic	-1.46	Neutral	0.480	Possibly Damaging	0.226	Benign	4.65	Benign	0.11	Tolerated			0.1780	0.1853		-4	-3	-7.0	53.05
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.145T>C	C49R 2D AIThe SynGAP1 missense variant C49R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain and no Foldetta (FoldX‑MD/Rosetta) result is available. Taken together, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-10.000	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.320	Likely Benign	-3.53	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.95	Benign	0.00	Affected			0.1605	0.2120		-4	-3	-7.0	53.05
c.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.1591T>C	C531R 2D AIThe SynGAP1 missense variant C531R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and polyPhen‑2 HumVar, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar classification because the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-12.600	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	2.0	-0.27	Likely Benign	0.02	Likely Benign	1.40	Destabilizing	0.619	Likely Pathogenic	-9.85	Deleterious	0.929	Possibly Damaging	0.385	Benign	-1.24	Pathogenic	0.00	Affected			0.1322	0.1566		-4	-3	-7.0	53.05
c.1636T>C	C546R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546R is 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 majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta return uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-15.237	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	-0.70	Ambiguous	0.3	2.04	Destabilizing	0.67	Ambiguous	1.70	Destabilizing	0.894	Likely Pathogenic	-9.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated			0.1808	0.1685		-4	-3	-7.0	53.05
c.1639T>C	C547R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while no tool in the dataset predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000					Uncertain		1				-16.967	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.76	Destabilizing	0.8	5.83	Destabilizing	6.80	Destabilizing	1.69	Destabilizing	0.900	Likely Pathogenic	-11.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.02	Affected	3.37	35	0.1802	0.1408		-4	-3	-7.0	53.05	267.4	-90.3	0.0	0.0	-0.1	0.1	X	X	X				X	Potentially Pathogenic	Cys547 is located in an α-helix (res. Ala533-Val560). The thiol side chain of Cys is situated in a hydrophobic inter-helix space, where it packs hydrophobically with other residues such as Ile626, Leu551, and Phe652. Additionally, the thiol side chain of Cys547 weakly hydrogen bonds with the carbonyl group of Leu543 in the same α-helix. In the variant simulations, the bulkier, positively charged guanidinium group of Arg547 must rotate out of the hydrophobic space. Consequently, it forms ionic interactions with the carboxylate groups of Glu548 in the same helix and Glu656 in the neighboring α-helix (res. Glu666-Asp644). This causes the two helices to slightly separate, significantly affecting the secondary structure integrity of the latter helix. These negative structural effects could be more pronounced during protein folding and are likely to be undermined in the MD simulations.
c.1654T>C	C552R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) yields an uncertain result, which is treated as unavailable evidence. Overall, the preponderance of predictions supports a pathogenic classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-14.315	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-1.18	Ambiguous	0.1	-0.51	Ambiguous	-0.85	Ambiguous	1.10	Destabilizing	0.809	Likely Pathogenic	-9.93	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.19	Pathogenic	0.48	Tolerated			0.1449	0.1366		-4	-3	-7.0	53.05
c.1675T>C	C559R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559R is not 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, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (six pathogenic vs five benign) lean toward a pathogenic interpretation, and this does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Thus, the variant is most likely pathogenic based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-9.509	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-1.03	Ambiguous	0.1	-0.38	Likely Benign	-0.71	Ambiguous	0.79	Ambiguous	0.498	Likely Benign	-8.58	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.46	Tolerated			0.2498	0.1720		-4	-3	-7.0	53.05
c.1726T>C	C576R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576R (ClinVar ID 2780076) is reported as Pathogenic and is not present in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. 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 it to be pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenicity. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among predictive tools and the high‑accuracy methods, the variant is most likely pathogenic, consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000					Pathogenic/Likely path.		2				-14.886	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	7.20	Destabilizing	1.0	4.09	Destabilizing	5.65	Destabilizing	1.64	Destabilizing	0.579	Likely Pathogenic	-10.88	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected	3.37	35	0.1887	0.1279		-3	-4	-7.0	53.05
c.1795T>C	C599R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599R is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a deleterious effect: REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, PROVEAN, ESM1b, FATHMM, premPS, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while FoldX reports an uncertain outcome. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-15.968	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.3	3.29	Destabilizing	2.15	Destabilizing	1.54	Destabilizing	0.909	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.1519	0.1566		-4	-3	-7.0	53.05
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.655T>C	C219R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, while the remaining 13 tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts Pathogenic. 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 no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000											-15.727	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.00	Destabilizing	1.5	2.20	Destabilizing	2.60	Destabilizing	1.33	Destabilizing	0.904	Likely Pathogenic	-9.90	Deleterious	0.969	Probably Damaging	0.680	Possibly Damaging	5.80	Benign	0.00	Affected			0.1381	0.1837		-4	-3	-7.0	53.05
c.688T>C	C230R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from FoldX and FATHMM, while pathogenic predictions are made by REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by Rosetta and Foldetta. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for C230R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-12.478	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	-0.48	Likely Benign	0.0	-1.61	Ambiguous	-1.05	Ambiguous	1.12	Destabilizing	0.905	Likely Pathogenic	-9.88	Deleterious	0.838	Possibly Damaging	0.548	Possibly Damaging	5.91	Benign	0.01	Affected			0.1744	0.1637		-4	-3	-7.0	53.05
c.697T>C	C233R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy methods, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD presence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-16.789	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.79	Destabilizing	3.4	2.17	Destabilizing	2.98	Destabilizing	1.75	Destabilizing	0.830	Likely Pathogenic	-10.68	Deleterious	0.002	Benign	0.002	Benign	5.71	Benign	0.01	Affected			0.1733	0.2212		-4	-3	-7.0	53.05
c.844T>C	C282R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282R is listed in ClinVar as Pathogenic (ClinVar ID 635755.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic outcome: FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Rosetta’s output is uncertain and is therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000					Pathogenic		2				-16.378	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.13	Destabilizing	0.6	1.58	Ambiguous	2.36	Destabilizing	1.70	Destabilizing	0.466	Likely Benign	-11.03	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.63	Pathogenic	0.00	Affected	3.39	18	0.1696	0.1557		-4	-3	-7.0	53.05	297.4	-98.2	-0.1	0.1	0.5	0.0	X		X				X	Potentially Pathogenic	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), is packed against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the bulky side chain of Arg282 with its positively charged guanidinium group is not suitable for this hydrophobic niche. Consequently, the hydrophobic residues must either make room to accommodate Arg282 or it must escape the hydrophobic C2 domain core.As a result, new hydrogen bonds are formed with the backbone carbonyl groups of the surrounding β sheet residues Ala399, Leu325, and His326, which decreases the unity of the secondary structure elements. Notably, it is likely that the residue swap causes major problems during the C2 domain folding that are not visible in the variant simulations. In fact, even increased lability in the C2 domain could adversely affect the establishment of a stable SynGAP-membrane association.
c.853T>C	C285R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. All other evaluated predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Consequently, the preponderance of evidence points to a pathogenic effect for C285R, 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	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.127	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	-0.47	Likely Benign	0.2	-0.63	Ambiguous	-0.55	Ambiguous	1.53	Destabilizing	0.583	Likely Pathogenic	-9.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1947	0.1453		-4	-3	-7.0	53.05
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.1106C>G	T369R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T369R is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438011‑C‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. Rosetta and Foldetta are uncertain, so their results are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also uncertain. Overall, the majority of evidence (nine benign vs two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.468512	Structured	0.437011	Uncertain	0.417	0.707	0.500								6-33438011-C-G	3	1.93e-6	-6.772	Likely Benign	0.571	Likely Pathogenic	Likely Benign	-0.27	Likely Benign	0.1	1.48	Ambiguous	0.61	Ambiguous	0.29	Likely Benign	0.148	Likely Benign	-2.15	Neutral	0.244	Benign	0.107	Benign	1.72	Pathogenic	0.32	Tolerated	3.42	19	0.1217	0.3737		-1	-1	-3.8	55.08
c.1223C>G	T408R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408R 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, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The premPS score is 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) as benign. With six benign versus seven pathogenic calls overall, the evidence is mixed, but the presence of two independent high‑accuracy benign predictions and the lack of ClinVar or gnomAD support suggests the variant is most likely benign, and this does not contradict any existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000											-12.075	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.1	-0.24	Likely Benign	-0.36	Likely Benign	0.79	Ambiguous	0.138	Likely Benign	-4.06	Deleterious	0.991	Probably Damaging	0.645	Possibly Damaging	4.12	Benign	0.15	Tolerated			0.1029	0.3180		-1	-1	-3.8	55.08
c.1373C>G	T458R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T458R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, and FATHMM, whereas a larger set—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. Uncertain results come from FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-12.984	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-0.81	Ambiguous	0.1	-0.11	Likely Benign	-0.46	Likely Benign	0.61	Ambiguous	0.390	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.52	Benign	0.20	Tolerated			0.1016	0.3013		-1	-1	-3.8	55.08
c.1463C>G	T488R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T488R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only FATHMM, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. 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 for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-14.353	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	1.29	Ambiguous	0.3	1.55	Ambiguous	1.42	Ambiguous	0.85	Ambiguous	0.726	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.22	Benign	0.00	Affected			0.0711	0.2048		-1	-1	-3.8	55.08
c.1595C>G	T532R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T532R missense variant is not listed in ClinVar and has no reported allele in gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default. FoldX and Rosetta provide uncertain results and are treated as unavailable. 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 effect. Overall, the balance of evidence (seven benign versus five pathogenic predictions) indicates that the variant is most likely benign, 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	0.275179	Structured	0.021478	Uncertain	0.889	0.385	0.000											-6.564	Likely Benign	0.608	Likely Pathogenic	Likely Benign	-0.57	Ambiguous	0.2	0.68	Ambiguous	0.06	Likely Benign	0.48	Likely Benign	0.495	Likely Benign	-2.62	Deleterious	0.694	Possibly Damaging	0.230	Benign	-1.20	Pathogenic	0.06	Tolerated			0.0841	0.1755		-1	-1	-3.8	55.08
c.2015C>G	T672R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results from Rosetta and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus indicates a likely pathogenic outcome. Overall, the majority of individual predictors lean toward pathogenicity, but the high‑accuracy tools provide conflicting benign signals. Therefore, 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	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000											-12.454	Likely Pathogenic	0.626	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.4	1.19	Ambiguous	0.36	Likely Benign	0.60	Ambiguous	0.084	Likely Benign	-4.47	Deleterious	0.886	Possibly Damaging	0.377	Benign	3.43	Benign	0.02	Affected			0.0996	0.2919		-1	-1	-3.8	55.08
c.2072C>G	T691R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, SGM Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-12.228	Likely Pathogenic	0.621	Likely Pathogenic	Likely Benign	-1.27	Ambiguous	0.3	-0.94	Ambiguous	-1.11	Ambiguous	1.35	Destabilizing	0.180	Likely Benign	-3.66	Deleterious	0.993	Probably Damaging	0.566	Possibly Damaging	3.48	Benign	0.02	Affected			0.0729	0.2478		-1	-1	-3.8	55.08
c.2168C>G	T723R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify it as benign. Two tools (polyPhen‑2 HumDiv and HumVar) predict it to be pathogenic, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign impact for T723R, 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	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-3.654	Likely Benign	0.408	Ambiguous	Likely Benign	-0.90	Ambiguous	0.1	-0.13	Likely Benign	-0.52	Ambiguous	0.44	Likely Benign	0.146	Likely Benign	-1.50	Neutral	0.931	Possibly Damaging	0.458	Possibly Damaging	3.51	Benign	0.29	Tolerated			0.0794	0.2437		-1	-1	-3.8	55.08
c.2465C>G	T822R 2D AIThe SynGAP1 missense variant T822R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (five pathogenic versus three benign predictions) suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											0.414	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-2.74	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	2.50	Benign	0.05	Affected			0.1182	0.3439		-1	-1	-3.8	55.08
c.2483C>G	T828R 2D AIThe SynGAP1 missense variant T828R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T828R, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-4.887	Likely Benign	0.773	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.38	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.64	Benign	0.47	Tolerated			0.0815	0.2530		-1	-1	-3.8	55.08
c.254C>G	T85R 2D AIThe SynGAP1 missense variant T85R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessment gives AlphaMissense‑Optimized a pathogenic score, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (benign)—leans toward benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the balance of evidence tilts toward a benign interpretation, with no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign, though the presence of pathogenic predictions from several tools indicates that further functional validation would be prudent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-7.936	In-Between	0.989	Likely Pathogenic	Likely Pathogenic										0.116	Likely Benign	-2.32	Neutral	0.813	Possibly Damaging	0.072	Benign	3.91	Benign	0.00	Affected			0.0754	0.2482		-1	-1	-3.8	55.08
c.2633C>G	T878R 2D AIThe SynGAP1 missense variant T878R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized 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 status because no ClinVar entry exists. 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											-4.289	Likely Benign	0.496	Ambiguous	Likely Benign										0.119	Likely Benign	-1.39	Neutral	0.611	Possibly Damaging	0.398	Benign	2.64	Benign	0.00	Affected			0.1006	0.2920		-1	-1	-3.8	55.08
c.2699C>G	T900R 2D AIThe SynGAP1 missense variant T900R is not reported 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, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.465347	Uncertain	0.289	0.924	0.375											-3.340	Likely Benign	0.617	Likely Pathogenic	Likely Benign										0.109	Likely Benign	0.34	Neutral	0.782	Possibly Damaging	0.530	Possibly Damaging	2.68	Benign	0.83	Tolerated			0.1027	0.2851		-1	-1	-3.8	55.08
c.2738C>G	T913R 2D AIThe SynGAP1 missense variant T913R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375											-3.218	Likely Benign	0.494	Ambiguous	Likely Benign										0.152	Likely Benign	-0.97	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.68	Benign	0.03	Affected			0.1025	0.3373		-1	-1	-3.8	55.08
c.3230C>G	T1077R 2D AIThe SynGAP1 missense variant T1077R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), which collectively classify the variant as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and no Foldetta stability assessment is available. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.988141	Binding	0.329	0.892	0.750											-4.109	Likely Benign	0.890	Likely Pathogenic	Ambiguous										0.121	Likely Benign	-1.01	Neutral	0.970	Probably Damaging	0.728	Possibly Damaging	4.18	Benign	0.03	Affected			0.1028	0.3491		-1	-1	-3.8	55.08
c.3419C>G	T1140R 2D AIThe SynGAP1 missense variant T1140R is listed in gnomAD (ID 6‑33444454‑C‑G) but has no ClinVar entry. 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; 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 status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.708094	Binding	0.293	0.854	1.000								6-33444454-C-G	1	6.20e-7	-4.245	Likely Benign	0.682	Likely Pathogenic	Likely Benign										0.073	Likely Benign	-1.69	Neutral	0.761	Possibly Damaging	0.398	Benign	2.61	Benign	0.15	Tolerated	4.32	4	0.0997	0.2442		-1	-1	-3.8	55.08
c.3428C>G	T1143R 2D AIThe SynGAP1 missense variant T1143R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools cluster into two groups: benign predictions include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. 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 favors benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of 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		0.919029	Disordered	0.722918	Binding	0.275	0.837	1.000											-2.882	Likely Benign	0.782	Likely Pathogenic	Likely Benign										0.175	Likely Benign	-2.31	Neutral	0.996	Probably Damaging	0.951	Probably Damaging	2.73	Benign	0.09	Tolerated			0.1087	0.3060		-1	-1	-3.8	55.08
c.3440C>G	T1147R 2D AIThe SynGAP1 missense variant T1147R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact for T1147R, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.746520	Binding	0.345	0.839	0.875											-3.234	Likely Benign	0.534	Ambiguous	Likely Benign										0.442	Likely Benign	-2.44	Neutral	0.411	Benign	0.139	Benign	5.46	Benign	0.01	Affected			0.1014	0.2742		-1	-1	-3.8	55.08
c.3461C>G	T1154R 2D AIThe SynGAP1 missense variant T1154R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that T1154R is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.464	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-4.05	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.0903	0.2101		-1	-1	-3.8	55.08
c.3914C>G	T1305R 2D AIThe SynGAP1 missense variant T1305R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.894658	Binding	0.390	0.873	0.875											-2.945	Likely Benign	0.194	Likely Benign	Likely Benign										0.220	Likely Benign	-1.33	Neutral	0.027	Benign	0.114	Benign	2.75	Benign	0.01	Affected			0.1115	0.3214		-1	-1	-3.8	55.08
c.3929C>G	T1310R 2D AIThe SynGAP1 missense variant T1310R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. Only SIFT predicts a damaging outcome, labeling it pathogenic. 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 this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Consequently, the aggregate evidence indicates that T1310R is most likely benign, 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		0.812494	Disordered	0.959076	Binding	0.398	0.904	0.750											-3.632	Likely Benign	0.226	Likely Benign	Likely Benign										0.231	Likely Benign	-0.59	Neutral	0.001	Benign	0.006	Benign	2.78	Benign	0.03	Affected			0.0844	0.2501		-1	-1	-3.8	55.08
c.3995C>G	T1332R 2D AIThe SynGAP1 missense variant T1332R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie and therefore unavailable; Foldetta results are not provided. Overall, the balance of evidence (five pathogenic versus three benign 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.			0.915074	Disordered	0.948427	Binding	0.442	0.754	0.875											-3.354	Likely Benign	0.878	Likely Pathogenic	Ambiguous										0.271	Likely Benign	-3.59	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	2.96	Benign	0.00	Affected			0.1173	0.3867		-1	-1	-3.8	55.08
c.431C>G	T144R 2D AIThe SynGAP1 missense variant T144R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-13.331	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous										0.177	Likely Benign	-2.83	Deleterious	0.609	Possibly Damaging	0.150	Benign	3.75	Benign	0.00	Affected			0.1188	0.2823		-1	-1	-3.8	55.08
c.668C>G	T223R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T223R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a mixed profile: benign calls come from FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic calls arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy consensus (SGM Consensus) favors pathogenicity (3/4 votes pathogenic), whereas Foldetta predicts benign stability. Because the majority of individual predictors lean benign and the high‑accuracy consensus is split, the overall assessment remains inconclusive. The variant is most likely benign, but the presence of several pathogenic predictions and the SGM Consensus result indicates that pathogenicity cannot be ruled out. This conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.070400	Structured	0.382605	Uncertain	0.867	0.316	0.125											-12.079	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	-0.36	Likely Benign	0.1	-0.27	Likely Benign	-0.32	Likely Benign	0.75	Ambiguous	0.827	Likely Pathogenic	-4.62	Deleterious	0.561	Possibly Damaging	0.178	Benign	5.73	Benign	0.06	Tolerated			0.0708	0.2407		-1	-1	-3.8	55.08
c.683C>G	T228R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T228R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-7.218	In-Between	0.965	Likely Pathogenic	Likely Pathogenic	-0.23	Likely Benign	0.1	0.69	Ambiguous	0.23	Likely Benign	0.67	Ambiguous	0.693	Likely Pathogenic	-3.40	Deleterious	0.952	Possibly Damaging	0.694	Possibly Damaging	5.60	Benign	0.01	Affected			0.1108	0.3405		-1	-1	-3.8	55.08
c.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.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.1022G>A	G341D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G341D is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID: 6-33437927‑G‑A). 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, FATHMM, and AlphaMissense‑Default. The remaining tools—Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta—return uncertain or inconclusive results and are treated as unavailable for pathogenicity inference. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Considering the majority of standard tools lean benign but the high‑accuracy consensus indicates pathogenicity, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250								6-33437927-G-A	6	3.72e-6	-7.402	In-Between	0.871	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.1	-1.32	Ambiguous	-0.52	Ambiguous	-0.04	Likely Benign	0.295	Likely Benign	-0.11	Neutral	0.454	Possibly Damaging	0.192	Benign	0.34	Pathogenic	0.25	Tolerated	3.42	13	0.1727	0.2241		-1	1	-3.1	58.04
c.1031G>A	G344D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G344D 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) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Based on the unanimous pathogenic predictions and the absence of benign calls, the variant is most likely pathogenic, 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	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250											-12.527	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	14.53	Destabilizing	1.5	11.36	Destabilizing	12.95	Destabilizing	1.13	Destabilizing	0.897	Likely Pathogenic	-6.30	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.49	Pathogenic	0.01	Affected			0.1572	0.1574		1	-1	-3.1	58.04
c.1109G>A	G370D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G370D is not 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, FATHMM, and AlphaMissense‑Default. The high‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, Foldetta (a folding‑stability method that integrates FoldX‑MD and Rosetta outputs) predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it yields an equal split of benign and pathogenic calls. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.461924	Structured	0.434325	Uncertain	0.359	0.720	0.500											-5.332	Likely Benign	0.597	Likely Pathogenic	Likely Benign	3.64	Destabilizing	3.8	0.83	Ambiguous	2.24	Destabilizing	0.30	Likely Benign	0.372	Likely Benign	-0.44	Neutral	0.007	Benign	0.001	Benign	1.32	Pathogenic	0.64	Tolerated			0.1632	0.1494		1	-1	-3.1	58.04
c.1127G>A	G376D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G376D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and ESM1b—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain stability change. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625											-7.125	In-Between	0.569	Likely Pathogenic	Likely Benign	3.10	Destabilizing	1.1	-1.08	Ambiguous	1.01	Ambiguous	0.52	Ambiguous	0.572	Likely Pathogenic	-1.05	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.09	Tolerated			0.1938	0.1235		1	-1	-3.1	58.04
c.1133G>A	G378D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G378D is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID 6‑33438038‑G‑A). Prediction tools that classify the variant as benign include premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Tools that predict pathogenicity are REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. ESM1b is uncertain, and no other high‑accuracy predictions are available. Overall, the majority of evidence supports a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625								6-33438038-G-A	1	6.97e-7	-7.767	In-Between	0.576	Likely Pathogenic	Likely Benign	11.41	Destabilizing	5.0	11.84	Destabilizing	11.63	Destabilizing	0.50	Likely Benign	0.619	Likely Pathogenic	-0.63	Neutral	1.000	Probably Damaging	0.992	Probably Damaging	1.32	Pathogenic	0.08	Tolerated	4.32	12	0.2130	0.2035		-1	1	-3.1	58.04
c.1151G>A	G384D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G384D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33438056‑G‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that predict pathogenicity are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; premPS is uncertain. Separately, the 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 majority of tools—including the high‑accuracy methods—indicate a pathogenic effect. This prediction does not contradict any 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	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750								6-33438056-G-A			-9.142	Likely Pathogenic	0.610	Likely Pathogenic	Likely Benign	2.06	Destabilizing	0.5	2.15	Destabilizing	2.11	Destabilizing	0.53	Ambiguous	0.439	Likely Benign	-0.93	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	2	0.2071	0.2235		-1	1	-3.1	58.04
c.1160G>A	G387D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G387D is reported in gnomAD (6‑33438065‑G‑A) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With two of the three high‑accuracy methods indicating pathogenicity and a majority of general predictors leaning toward pathogenic, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.642678	Disordered	0.422910	Uncertain	0.293	0.861	0.750								6-33438065-G-A	2	1.24e-6	-8.625	Likely Pathogenic	0.612	Likely Pathogenic	Likely Benign	3.57	Destabilizing	2.3	3.22	Destabilizing	3.40	Destabilizing	0.39	Likely Benign	0.459	Likely Benign	-0.37	Neutral	0.069	Benign	0.041	Benign	1.32	Pathogenic	0.02	Affected	4.32	3	0.2145	0.2035		-1	1	-3.1	58.04
c.1163G>A	G388D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388D is reported in gnomAD (variant ID 6-33438068‑G‑A) but has no entry in ClinVar. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions arise from SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments reinforce this split: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic; Foldetta, integrating FoldX‑MD and Rosetta outputs, also predicts a pathogenic impact on protein stability. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for G388D, 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	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750								6-33438068-G-A			-8.416	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	5.56	Destabilizing	7.3	3.08	Destabilizing	4.32	Destabilizing	0.42	Likely Benign	0.618	Likely Pathogenic	-0.67	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	3	0.1923	0.1624		-1	1	-3.1	58.04
c.1172G>A	G391D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G391D is 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, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools, Rosetta and Foldetta, return uncertain results. High‑accuracy methods give a benign call from AlphaMissense‑Optimized; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is also inconclusive. Overall, six tools favor pathogenicity while five favor benignity, with two uncertain. Thus, the variant is most likely pathogenic based on the current computational evidence, 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.		C2	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750											-4.651	Likely Benign	0.674	Likely Pathogenic	Likely Benign	2.59	Destabilizing	1.1	1.26	Ambiguous	1.93	Ambiguous	0.22	Likely Benign	0.562	Likely Pathogenic	-0.95	Neutral	0.999	Probably Damaging	0.960	Probably Damaging	1.32	Pathogenic	0.29	Tolerated			0.1900	0.1305		1	-1	-3.1	58.04
c.1178G>A	G393D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G393D 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 SIFT, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports a benign outcome, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable. Overall, the preponderance of evidence points to a pathogenic effect for G393D, 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	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625											-5.247	Likely Benign	0.717	Likely Pathogenic	Likely Benign	3.30	Destabilizing	1.4	-1.00	Ambiguous	1.15	Ambiguous	0.57	Ambiguous	0.528	Likely Pathogenic	-2.60	Deleterious	0.991	Probably Damaging	0.831	Possibly Damaging	1.32	Pathogenic	0.19	Tolerated			0.2077	0.1645		1	-1	-3.1	58.04
c.1187G>A	G396D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G396D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, whereas only AlphaMissense‑Default predicts a pathogenic outcome. Tools that assess protein stability (FoldX, Rosetta, Foldetta) yield uncertain or inconclusive results. High‑accuracy consensus methods reinforce the benign assessment: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports “Likely Benign”; AlphaMissense‑Optimized also predicts benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Based on the preponderance of 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	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500											-4.148	Likely Benign	0.678	Likely Pathogenic	Likely Benign	1.92	Ambiguous	0.8	1.33	Ambiguous	1.63	Ambiguous	0.17	Likely Benign	0.272	Likely Benign	-1.49	Neutral	0.421	Benign	0.080	Benign	3.91	Benign	0.35	Tolerated			0.1702	0.1122		1	-1	-3.1	58.04
c.1211C>A	A404E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A404E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.232838	Structured	0.415505	Uncertain	0.965	0.355	0.000											-13.639	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.1	3.04	Destabilizing	2.60	Destabilizing	1.51	Destabilizing	0.163	Likely Benign	-2.77	Deleterious	0.179	Benign	0.033	Benign	4.02	Benign	0.02	Affected			0.1423	0.2383		0	-1	-5.3	58.04
c.1262C>A	A421E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic calls are made by ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Rosetta, premPS, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods give mixed results: FoldX is uncertain, Foldetta is uncertain, and Rosetta alone predicts pathogenic. 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 remains uncertain. Overall, the majority of evidence, including the high‑accuracy tools, points to a pathogenic impact for A421E, 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	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-11.993	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.2	2.07	Destabilizing	1.35	Ambiguous	1.30	Destabilizing	0.233	Likely Benign	-4.24	Deleterious	0.368	Benign	0.144	Benign	3.44	Benign	0.14	Tolerated			0.1288	0.1830		0	-1	-5.3	58.04
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.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.1328G>A	G443D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443D is not 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, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome. Uncertain results 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 points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing clinical data. 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.	Likely Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-6.818	Likely Benign	0.761	Likely Pathogenic	Likely Benign	-0.19	Likely Benign	0.2	-1.72	Ambiguous	-0.96	Ambiguous	0.32	Likely Benign	0.072	Likely Benign	-0.50	Neutral	0.345	Benign	0.072	Benign	3.63	Benign	0.43	Tolerated			0.1687	0.2090		1	-1	-3.1	58.04
c.1349C>A	A450E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A450E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include SIFT and FATHMM, whereas the majority of tools predict it to be pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No predictions are inconclusive. Overall, the evidence strongly favors a pathogenic impact for A450E, which does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000					Uncertain		1				-16.578	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	3.86	Destabilizing	0.2	5.23	Destabilizing	4.55	Destabilizing	1.59	Destabilizing	0.653	Likely Pathogenic	-4.67	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.38	Benign	0.07	Tolerated	3.37	32	0.0823	0.1695		0	-1	-5.3	58.04	240.1	-82.6	0.0	0.0	0.7	0.0			X				X	Potentially Pathogenic	The methyl group of Ala450, located in an α helix (res. Asn440-Thr458), packs against hydrophobic residues in the inter-helix space (e.g., Leu692). In the variant simulations, the carboxylate group of the Glu450 side chain rotates outward, away from the hydrophobic niche, where it does not form any lasting salt bridges or H-bonds. Although the residue swap does not negatively affect the protein structure based on the simulations, it is possible that the introduction of the negatively charged residue adversely affects the folding process or tertiary assembly.
c.1376G>A	G459D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G459D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate benign effects include REVEL and FATHMM, while the majority of tools predict pathogenicity: FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, Foldetta, and premPS. 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 evidence points to a pathogenic effect for G459D, and this conclusion does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-11.258	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.21	Destabilizing	0.1	0.56	Ambiguous	1.39	Ambiguous	0.93	Ambiguous	0.454	Likely Benign	-6.18	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.07	Benign	0.05	Affected			0.1466	0.1905		1	-1	-3.1	58.04
c.1505G>A	G502D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502D is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. Based on the uniform predictions, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000					Uncertain		1				-14.796	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.79	Destabilizing	0.9	5.69	Destabilizing	4.74	Destabilizing	1.38	Destabilizing	0.915	Likely Pathogenic	-6.80	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	-1.66	Pathogenic	0.00	Affected	3.37	35	0.1715	0.1172		1	-1	-3.1	58.04	224.2	-80.0	-0.8	0.7	0.6	0.3	X		X				X	Potentially Pathogenic	Gly502 is located in a hinge in the middle of an α-helix (res. Leu489-Glu519). In the WT, Gly502 acts as an α-helix breaker due to its lack of a side chain, facilitating a bend in the middle of the α-helix. In the variant simulations, the carboxylate group of Asp502 forms hydrogen bonds with neighboring residues (e.g., Ser677, Lys504), disrupting the hinge. Additionally, Asp502 struggles to fit into the α-helix hinge and cannot generate a similar bend as Gly502, which would drastically affect the secondary structure during folding. Thus, the deleterious effect seen in the simulations is likely an underestimate of the impact of the residue swap on the protein structure during protein folding.
c.1598C>A	A533E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533E is not 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, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM, while AlphaMissense‑Default remains 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 as benign. Overall, the majority of evidence points to a benign impact. 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.		GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-10.810	Likely Pathogenic	0.553	Ambiguous	Likely Benign	-0.13	Likely Benign	0.0	-0.26	Likely Benign	-0.20	Likely Benign	0.43	Likely Benign	0.314	Likely Benign	-1.89	Neutral	0.259	Benign	0.107	Benign	-1.18	Pathogenic	0.18	Tolerated			0.1147	0.1498		0	-1	-5.3	58.04
c.1610C>A	A537E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing or inconclusive. Based on the overall consensus of the available tools, 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.		GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000											-5.120	Likely Benign	0.450	Ambiguous	Likely Benign	-0.14	Likely Benign	0.1	0.00	Likely Benign	-0.07	Likely Benign	0.23	Likely Benign	0.378	Likely Benign	-1.78	Neutral	0.987	Probably Damaging	0.838	Possibly Damaging	-1.04	Pathogenic	1.00	Tolerated			0.1347	0.1566		0	-1	-5.3	58.04
c.1730C>A	A577E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A577E 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 REVEL, FoldX, PROVEAN, and SIFT, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain; Rosetta and premPS are inconclusive. Overall, the majority of evaluated tools (five pathogenic vs. four benign) and the SGM‑Consensus support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.019074	Uncertain	0.913	0.239	0.000											-9.607	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.72	Ambiguous	0.51	Ambiguous	0.62	Ambiguous	0.419	Likely Benign	-1.91	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	-1.12	Pathogenic	0.76	Tolerated			0.1487	0.1799		0	-1	-5.3	58.04
c.1739G>A	G580D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580D is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS and Rosetta are uncertain. High‑accuracy tools reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No benign predictions are present. Consequently, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-10.086	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.1	1.39	Ambiguous	2.12	Destabilizing	0.83	Ambiguous	0.712	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.25	Pathogenic	0.04	Affected			0.1793	0.1971		1	-1	-3.1	58.04
c.1754C>A	A585E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A585E is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools cluster into two groups: the single benign call comes from SIFT, while all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label the change as pathogenic or likely pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports pathogenic. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-14.715	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	5.38	Destabilizing	0.7	3.70	Destabilizing	4.54	Destabilizing	1.42	Destabilizing	0.539	Likely Pathogenic	-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.30	Pathogenic	0.28	Tolerated			0.1160	0.1212		0	-1	-5.3	58.04
c.1802C>A	A601E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A601E is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity largely agree: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000					Conflicting		2				-16.752	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	6.68	Destabilizing	0.8	5.76	Destabilizing	6.22	Destabilizing	1.24	Destabilizing	0.588	Likely Pathogenic	-4.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.54	Benign	0.00	Affected	3.37	35	0.1346	0.1444		0	-1	-5.3	58.04	240.0	-82.3	0.0	0.0	0.7	0.1		X	X				X	Potentially Pathogenic	The methyl side chain of Ala601, located on an α helix (res. Glu582-Met603), packs hydrophobically against other hydrophobic residues in the inter-helix space (e.g., Phe597, Leu598, Leu506, Phe608).In the variant simulations, the carboxylate group of Glu601 faces the inter-helix space and is forced to shift slightly away from the hydrophobic niche. Additionally, in two of the simulations, Glu601 forms a salt bridge with Arg499, causing the otherwise stable salt bridge between Arg499 and Glu496 at the outer surface of an α helix (res. Leu489-Glu519) to break due to the residue swap.These effects suggest that the protein folding process could be seriously affected. Moreover, due to its location at the GAP-Ras interface, it could also impact the complex formation with the GTPase.
c.1940G>A	G647D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G647D is reported in ClinVar as having no entry and is present in gnomAD (6‑33441199‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized all predict benign. Only AlphaMissense‑Default predicts pathogenic, while FoldX, Foldetta, premPS, and ESM1b are uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields benign; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the consensus of most tools and the high‑accuracy predictions indicate that G647D is most likely benign, and this is consistent with the absence of a pathogenic ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000								6-33441199-G-A	1	6.20e-7	-7.643	In-Between	0.582	Likely Pathogenic	Likely Benign	0.68	Ambiguous	0.1	0.33	Likely Benign	0.51	Ambiguous	0.56	Ambiguous	0.098	Likely Benign	-1.63	Neutral	0.282	Benign	0.128	Benign	3.45	Benign	0.24	Tolerated	3.37	30	0.1630	0.1372		-1	1	-3.1	58.04
c.1973G>A	G658D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G658D is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6-33441232‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only PROVEAN predicts a pathogenic outcome, while Rosetta, Foldetta, ESM1b, and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta, which integrates FoldX‑MD and Rosetta, is also inconclusive. Overall, the preponderance of evidence points to a benign effect, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000					Uncertain		1	6-33441232-G-A	3	1.86e-6	-7.786	In-Between	0.442	Ambiguous	Likely Benign	-0.40	Likely Benign	0.1	-0.59	Ambiguous	-0.50	Ambiguous	0.46	Likely Benign	0.144	Likely Benign	-2.64	Deleterious	0.008	Benign	0.005	Benign	3.53	Benign	0.38	Tolerated	3.39	24	0.2106	0.2333		1	-1	-3.1	58.04	219.8	-84.3	0.0	0.0	0.2	0.1						X		Potentially Pathogenic	Gly658, located on the outer surface of an α helix (res. Ser641-Glu666), weakens the helix integrity at that spot, which is necessary for the kink in the middle of the long helix. In the variant simulations, the carboxylic acid side chain of Asp658 is on the surface of the α helix and is not involved in any interactions. However, aspartate is not as effective a breaker of the secondary structure element as glycine, which may lead to misfolding.
c.2042G>A	G681D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas the remaining 11 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all predict pathogenicity. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized returns a pathogenic classification; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. premPS is inconclusive and is treated as unavailable. Taken together, the overwhelming majority of evidence points to a pathogenic impact for G681D. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.451	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	1.5	4.54	Destabilizing	3.58	Destabilizing	0.96	Ambiguous	0.471	Likely Benign	-6.98	Deleterious	0.999	Probably Damaging	0.840	Possibly Damaging	3.45	Benign	0.00	Affected			0.1697	0.1695		1	-1	-3.1	58.04
c.2057G>A	G686D 2D AIThe SynGAP1 missense variant G686D is 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. 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 for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-14.109	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.00	Destabilizing	1.7	2.61	Destabilizing	2.31	Destabilizing	1.05	Destabilizing	0.563	Likely Pathogenic	-6.28	Deleterious	1.000	Probably Damaging	0.967	Probably Damaging	3.40	Benign	0.00	Affected			0.1720	0.2196		1	-1	-3.1	58.04
c.2135G>A	G712D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712D is catalogued in gnomAD (ID 6‑33441600‑G‑A) but has no ClinVar entry. In silico predictors show mixed results: benign calls come from REVEL, SIFT, and FATHMM, while pathogenic calls are made by FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain predictions are reported by premPS and AlphaMissense‑Optimized. The high‑accuracy consensus tools give a pathogenic verdict: AlphaMissense‑Optimized is inconclusive, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Overall, the majority of reliable predictors and the consensus methods lean toward a pathogenic effect, and this assessment does not conflict with ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000								6-33441600-G-A	1	6.20e-7	-8.211	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.87	Destabilizing	0.1	5.37	Destabilizing	4.12	Destabilizing	0.90	Ambiguous	0.320	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.12	Tolerated	3.50	9	0.2146	0.2533		-1	1	-3.1	58.04
c.2270G>A	G757D 2D AIThe SynGAP1 missense variant G757D 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 high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Taken together, the preponderance of evidence supports a benign interpretation, and this assessment does not contradict any ClinVar annotation (none is present). Therefore, the variant is most likely benign, with no conflict with ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.830995	Binding	0.310	0.869	0.375											-4.613	Likely Benign	0.387	Ambiguous	Likely Benign										0.150	Likely Benign	-0.90	Neutral	0.454	Possibly Damaging	0.192	Benign	2.71	Benign	0.11	Tolerated			0.1826	0.1611		1	-1	-3.1	58.04
c.2327G>A	G776D 2D AIThe SynGAP1 missense variant G776D is catalogued in gnomAD (ID 6‑33442485‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates benign. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G776D, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442485-G-A			0.388	Likely Benign	0.566	Likely Pathogenic	Likely Benign										0.188	Likely Benign	0.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.30	Benign	0.10	Tolerated	3.64	6	0.1835	0.2971		-1	1	-3.1	58.04
c.2399G>A	G800D 2D AIThe SynGAP1 missense variant G800D is catalogued in gnomAD (6-33442951‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (derived from the majority of the four high‑accuracy predictors) also yields a benign verdict. Foldetta results are unavailable, so they do not influence the assessment. Overall, the evidence strongly supports a benign classification, 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	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625								6-33442951-G-A			-5.929	Likely Benign	0.400	Ambiguous	Likely Benign										0.088	Likely Benign	-0.84	Neutral	0.451	Benign	0.265	Benign	2.76	Benign	0.34	Tolerated	4.32	2	0.1664	0.1877		-1	1	-3.1	58.04
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.2405G>A	G802D 2D AIThe SynGAP1 missense variant G802D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (6‑33442957‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the change as benign. No tool predicts a pathogenic outcome. The high‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625					Uncertain		1	6-33442957-G-A	1	6.20e-7	-5.083	Likely Benign	0.476	Ambiguous	Likely Benign										0.153	Likely Benign	-0.38	Neutral	0.126	Benign	0.138	Benign	2.72	Benign	0.09	Tolerated	3.77	5	0.1993	0.2742		1	-1	-3.1	58.04
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.2543G>A	G848D 2D AIThe SynGAP1 missense variant G848D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500											-0.059	Likely Benign	0.318	Likely Benign	Likely Benign										0.121	Likely Benign	2.94	Neutral	0.008	Benign	0.019	Benign	2.95	Benign	0.81	Tolerated			0.1702	0.1392		1	-1	-3.1	58.04
c.2555G>A	G852D 2D AIThe SynGAP1 missense variant G852D is catalogued in gnomAD (ID 6‑33443107‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for G852D, and this conclusion is not contradicted by any ClinVar annotation (none is present). 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								6-33443107-G-A	1	6.20e-7	-5.588	Likely Benign	0.203	Likely Benign	Likely Benign										0.154	Likely Benign	0.67	Neutral	0.001	Benign	0.005	Benign	4.18	Benign	0.01	Affected	3.77	5	0.1855	0.2175		-1	1	-3.1	58.04
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.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.2636C>A	A879E 2D AIThe SynGAP1 missense variant A879E is reported in gnomAD (variant ID 6‑33443188‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default 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 specifically show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data is missing. Overall, the majority of evidence points to a benign effect, 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 Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250								6-33443188-C-A	1	6.20e-7	-3.786	Likely Benign	0.503	Ambiguous	Likely Benign										0.070	Likely Benign	-0.27	Neutral	0.872	Possibly Damaging	0.659	Possibly Damaging	2.70	Benign	0.27	Tolerated	3.77	5	0.1120	0.1903		-1	0	-5.3	58.04
c.2657C>A	A886E 2D AIThe SynGAP1 missense variant A886E is not 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 and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, 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. 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.			0.716283	Disordered	0.619166	Binding	0.359	0.922	0.500											-3.747	Likely Benign	0.422	Ambiguous	Likely Benign										0.096	Likely Benign	-1.31	Neutral	0.423	Benign	0.230	Benign	2.17	Pathogenic	0.00	Affected			0.1483	0.2008		0	-1	-5.3	58.04
c.2687G>A	G896D 2D AIThe SynGAP1 missense variant G896D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Consequently, the evidence is evenly split between benign and pathogenic predictions, with no decisive support from the most reliable methods. The variant is therefore classified as of uncertain significance; it does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625											-4.500	Likely Benign	0.905	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-2.39	Neutral	0.997	Probably Damaging	0.934	Probably Damaging	2.44	Pathogenic	0.16	Tolerated			0.1707	0.1842		1	-1	-3.1	58.04
c.2702C>A	A901E 2D AIThe SynGAP1 missense variant A901E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while 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		0.595080	Disordered	0.489838	Uncertain	0.306	0.917	0.375											-4.350	Likely Benign	0.802	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-0.53	Neutral	0.800	Possibly Damaging	0.300	Benign	2.64	Benign	0.12	Tolerated			0.1433	0.2424		0	-1	-5.3	58.04
c.2708G>A	G903D 2D AIThe SynGAP1 missense variant G903D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375											-4.481	Likely Benign	0.849	Likely Pathogenic	Ambiguous										0.137	Likely Benign	-1.85	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.1535	0.1321		1	-1	-3.1	58.04
c.2729G>A	G910D 2D AIThe SynGAP1 missense variant G910D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250											-4.190	Likely Benign	0.856	Likely Pathogenic	Ambiguous										0.214	Likely Benign	-1.87	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.84	Benign	0.05	Affected			0.1642	0.1477		1	-1	-3.1	58.04
c.2744G>A	G915D 2D AIThe SynGAP1 missense variant G915D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G915D, 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		0.657645	Disordered	0.808641	Binding	0.302	0.880	0.375											-3.409	Likely Benign	0.502	Ambiguous	Likely Benign										0.134	Likely Benign	-1.75	Neutral	0.978	Probably Damaging	0.871	Possibly Damaging	2.70	Benign	0.01	Affected			0.1574	0.1559		1	-1	-3.1	58.04
c.2819G>A	G940D 2D AIThe SynGAP1 missense variant G940D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443371‑G‑A). 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 and polyPhen‑2 HumVar. Two tools, AlphaMissense‑Default and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it receives two benign and two uncertain votes, and Foldetta’s protein‑folding stability analysis is unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625								6-33443371-G-A	6	3.72e-6	-7.311	In-Between	0.397	Ambiguous	Likely Benign										0.076	Likely Benign	-0.68	Neutral	0.770	Possibly Damaging	0.583	Possibly Damaging	2.72	Benign	0.17	Tolerated	3.77	5	0.1837	0.2252		-1	1	-3.1	58.04
c.2828G>A	G943D 2D AIThe SynGAP1 missense variant G943D is not reported in ClinVar and is absent from gnomAD. In silico predictors that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “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. Taken together, the overwhelming majority of predictions indicate a benign effect, and this conclusion does not contradict any ClinVar status (none is assigned). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.973328	Disordered	0.860437	Binding	0.372	0.910	0.750											-7.951	In-Between	0.304	Likely Benign	Likely Benign										0.296	Likely Benign	-0.28	Neutral	0.224	Benign	0.113	Benign	2.85	Benign	0.11	Tolerated			0.1904	0.2826		1	-1	-3.1	58.04
c.2831G>A	G944D 2D AIThe SynGAP1 missense variant G944D is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools largely support a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the majority‑vote SGM‑Consensus also indicates a likely benign outcome. Only SIFT predicts a pathogenic effect, and ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign classification. Foldetta stability analysis is not available for this residue. Overall, the preponderance of evidence points to a benign impact, and this assessment does not conflict with the absence of a ClinVar claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750											-7.684	In-Between	0.296	Likely Benign	Likely Benign										0.421	Likely Benign	-1.42	Neutral	0.224	Benign	0.131	Benign	3.70	Benign	0.00	Affected			0.1833	0.2826		1	-1	-3.1	58.04
c.2843G>A	G948D 2D AIThe SynGAP1 missense variant G948D 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750											-8.423	Likely Pathogenic	0.267	Likely Benign	Likely Benign										0.279	Likely Benign	0.15	Neutral	0.818	Possibly Damaging	0.266	Benign	4.55	Benign	0.11	Tolerated			0.1871	0.2826		1	-1	-3.1	58.04
c.2846G>A	G949D 2D AIThe SynGAP1 missense variant G949D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (5 pathogenic vs. 4 benign) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750											-8.692	Likely Pathogenic	0.239	Likely Benign	Likely Benign										0.316	Likely Benign	0.25	Neutral	0.945	Possibly Damaging	0.753	Possibly Damaging	2.21	Pathogenic	0.02	Affected			0.1927	0.2826		1	-1	-3.1	58.04
c.2849G>A	G950D 2D AIThe SynGAP1 missense variant G950D is not 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), AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign outcome. Foldetta, a protein‑folding stability method, 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 status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.888649	Binding	0.368	0.923	0.750											-7.515	In-Between	0.245	Likely Benign	Likely Benign										0.402	Likely Benign	-0.61	Neutral	0.411	Benign	0.131	Benign	2.26	Pathogenic	0.02	Affected			0.1874	0.2826		1	-1	-3.1	58.04
c.2855G>A	G952D 2D AIThe SynGAP1 missense variant G952D is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools overwhelmingly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments corroborate the benign trend: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.910621	Binding	0.341	0.926	0.750											-7.299	In-Between	0.274	Likely Benign	Likely Benign										0.241	Likely Benign	-0.75	Neutral	0.033	Benign	0.015	Benign	3.20	Benign	0.05	Affected			0.1928	0.2826		1	-1	-3.1	58.04