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.1288A>G	M430V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated changes. Only polyPhen‑2 HumDiv flags it as pathogenic, while the SGM‑Consensus score is Likely Benign. Stability‑based methods are inconclusive: FoldX and premPS return Uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports Uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta remains Uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-3.555	Likely Benign	0.091	Likely Benign	Likely Benign	1.48	Ambiguous	0.1	-0.23	Likely Benign	0.63	Ambiguous	0.87	Ambiguous	0.103	Likely Benign	-1.35	Neutral	0.918	Possibly Damaging	0.185	Benign	3.53	Benign	0.51	Tolerated			0.3397	0.4953		2	1	2.3	-32.06
c.1294T>A	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.496	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1295G>C	C432S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification for C432S, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-8.229	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.1	0.96	Ambiguous	0.79	Ambiguous	1.52	Destabilizing	0.417	Likely Benign	-9.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.12	Tolerated			0.4262	0.1415		0	-1	-3.3	-16.06
c.1300G>A	V434I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434I (ClinVar ID 212346.0, status Uncertain) is present in gnomAD (ID 6‑33438205‑G‑A). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000					Uncertain		1	6-33438205-G-A	1	6.19e-7	-6.999	Likely Benign	0.129	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	0.22	Likely Benign	0.09	Likely Benign	0.31	Likely Benign	0.192	Likely Benign	-0.82	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.53	Benign	0.18	Tolerated	3.37	29	0.0675	0.3415		4	3	0.3	14.03	246.7	-27.7	0.0	0.0	0.1	0.0						X		Potentially Benign	The iso-propyl side chain of Val434, located at the end of an α helix (res. Met414-Glu436), packs against hydrophobic residues in an interhelix space (e.g., Met430, Ala707, Leu711). In the variant simulations, the sec-butyl group of Ile434 is able to form the same hydrophobic interactions. Accordingly, the residue swap does not negatively affect the protein structure based on the simulations.
c.1319A>G	N440S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or likely benign. Only FoldX and premPS returned uncertain results, which are treated as unavailable. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Consequently, 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	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-1.753	Likely Benign	0.058	Likely Benign	Likely Benign	0.52	Ambiguous	0.1	0.08	Likely Benign	0.30	Likely Benign	-0.50	Ambiguous	0.104	Likely Benign	1.15	Neutral	0.001	Benign	0.000	Benign	3.53	Benign	0.92	Tolerated			0.2024	0.3556		1	1	2.7	-27.03
c.1358A>G	H453R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H453R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an inconclusive result because FoldX is uncertain and Rosetta is benign. Overall, the balance of evidence favors a pathogenic interpretation, 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	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-9.239	Likely Pathogenic	0.573	Likely Pathogenic	Likely Benign	-0.52	Ambiguous	0.1	0.37	Likely Benign	-0.08	Likely Benign	0.56	Ambiguous	0.396	Likely Benign	-7.91	Deleterious	0.993	Probably Damaging	0.957	Probably Damaging	3.53	Benign	0.39	Tolerated			0.1646	0.2031		2	0	-1.3	19.05
c.1426T>C	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.196	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>A	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>G	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438460‑C‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that returned uncertain results—FoldX, Rosetta, Foldetta, and premPS—do not contribute to the assessment. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, with two pathogenic and two benign calls; Foldetta also reports an uncertain stability change. Overall, the balance of evidence favors a pathogenic effect for F476L, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000					Uncertain		2	6-33438460-C-G	4	2.48e-6	-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1434A>C	E478D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478D is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-1.004	Likely Benign	0.085	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	-0.65	Ambiguous	-0.35	Likely Benign	-0.28	Likely Benign	0.175	Likely Benign	0.55	Neutral	0.000	Benign	0.001	Benign	3.53	Benign	0.70	Tolerated			0.1768	0.3315		3	2	0.0	-14.03
c.1434A>T	E478D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478D is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-1.004	Likely Benign	0.085	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	-0.65	Ambiguous	-0.35	Likely Benign	-0.28	Likely Benign	0.175	Likely Benign	0.55	Neutral	0.000	Benign	0.001	Benign	3.53	Benign	0.70	Tolerated			0.1768	0.3315		3	2	0.0	-14.03
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.2023A>G	N675D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments give AlphaMissense‑Optimized a benign call, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) a pathogenic call, and Foldetta an uncertain result. With an equal split of general predictions but a pathogenic majority in the high‑accuracy consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-12.829	Likely Pathogenic	0.497	Ambiguous	Likely Benign	1.41	Ambiguous	0.4	-0.26	Likely Benign	0.58	Ambiguous	1.05	Destabilizing	0.246	Likely Benign	-3.87	Deleterious	0.997	Probably Damaging	0.865	Possibly Damaging	3.53	Benign	0.17	Tolerated			0.1914	0.4901		2	1	0.0	0.98
c.2090G>C	W697S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697S is not 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as unavailable due to uncertainty. Overall, the majority of evidence 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.		GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-4.900	Likely Benign	0.449	Ambiguous	Likely Benign	1.90	Ambiguous	0.1	1.58	Ambiguous	1.74	Ambiguous	1.13	Destabilizing	0.322	Likely Benign	-8.89	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	3.53	Benign	0.13	Tolerated			0.3738	0.1089		-2	-3	0.1	-99.14
c.2110A>C	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in gnomAD and has no ClinVar entry. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. FoldX, Rosetta, and Foldetta provide uncertain stability results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the evidence points to the variant being 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	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.178	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2112C>A	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no additional evidence. Overall, the preponderance of evidence from multiple independent predictors indicates that S704R is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2112C>G	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). FoldX and Rosetta give uncertain results, and Foldetta (a combined FoldX‑MD/Rosetta stability assessment) is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2144C>G	P715R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715R 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 (SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Because the pathogenic predictions outnumber the benign ones and the high‑accuracy consensus supports a deleterious effect, 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	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-12.191	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	2.19	Destabilizing	0.1	0.53	Ambiguous	1.36	Ambiguous	0.87	Ambiguous	0.324	Likely Benign	-8.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.01	Affected			0.1389	0.2620		0	-2	-2.9	59.07
c.2188A>C	I730L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730L is reported as “Likely Benign” in ClinVar and is not present in gnomAD. All available in‑silico predictors classify the change as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status. 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											-1.681	Likely Benign	0.069	Likely Benign	Likely Benign	-0.05	Likely Benign	0.0	-0.31	Likely Benign	-0.18	Likely Benign	-0.17	Likely Benign	0.028	Likely Benign	-0.63	Neutral	0.000	Benign	0.005	Benign	3.53	Benign	0.47	Tolerated			0.0739	0.2869		2	2	-0.7	0.00
c.398T>A	L133Q 2D AIThe SynGAP1 missense variant L133Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-9.054	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-2.65	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.01	Affected			0.1316	0.0879		-2	-2	-7.3	14.97
c.413A>T	K138I 2D AIThe SynGAP1 missense variant K138I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-9.366	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.295	Likely Benign	-4.74	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.00	Affected			0.1003	0.3054		-2	-3	8.4	-15.01
c.428G>A	R143Q 2D AIThe SynGAP1 missense variant R143Q is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33432725‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta stability analysis is unavailable. Overall, the majority of predictions (5 pathogenic vs 4 benign) and the pathogenic call from AlphaMissense‑Optimized suggest that the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625								6-33432725-G-A	2	1.35e-6	-12.110	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-2.48	Neutral	0.678	Possibly Damaging	0.176	Benign	3.53	Benign	0.00	Affected	3.61	5	0.3255	0.2678		1	1	1.0	-28.06
c.446A>T	K149I 2D AIThe SynGAP1 missense variant K149I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-14.426	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-4.72	Deleterious	0.535	Possibly Damaging	0.403	Benign	3.53	Benign	0.00	Affected			0.1477	0.3965		-2	-3	8.4	-15.01
c.1290G>A	M430I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430I is catalogued in gnomAD (6‑33438195‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign. 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	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000								6-33438195-G-A	1	6.19e-7	-4.655	Likely Benign	0.420	Ambiguous	Likely Benign	1.22	Ambiguous	0.1	-0.29	Likely Benign	0.47	Likely Benign	0.65	Ambiguous	0.068	Likely Benign	-1.62	Neutral	0.134	Benign	0.025	Benign	3.54	Benign	0.40	Tolerated	3.37	29	0.1524	0.4116		1	2	2.6	-18.03
c.1290G>C	M430I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the remaining predictions (FoldX, premPS, AlphaMissense‑Default) are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also classifies the variant as benign. Taken together, the consensus of both general and high‑accuracy predictors is that M430I is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-4.655	Likely Benign	0.420	Ambiguous	Likely Benign	1.22	Ambiguous	0.1	-0.29	Likely Benign	0.47	Likely Benign	0.65	Ambiguous	0.068	Likely Benign	-1.62	Neutral	0.134	Benign	0.025	Benign	3.54	Benign	0.40	Tolerated	3.37	29	0.1524	0.4116		1	2	2.6	-18.03
c.1290G>T	M430I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. Predictions that are inconclusive are FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, while Foldetta’s combined FoldX‑MD/Rosetta output is unavailable due to the uncertain FoldX result. Overall, the evidence overwhelmingly supports a benign classification for M430I, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-4.655	Likely Benign	0.420	Ambiguous	Likely Benign	1.22	Ambiguous	0.1	-0.29	Likely Benign	0.47	Likely Benign	0.65	Ambiguous	0.068	Likely Benign	-1.62	Neutral	0.134	Benign	0.025	Benign	3.54	Benign	0.40	Tolerated	3.37	29	0.1524	0.4116		1	2	2.6	-18.03
c.1335G>C	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is reported in gnomAD (ID 6‑33438240‑G‑C) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence, especially the SGM Consensus, points to a pathogenic effect for E445D. 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000								6-33438240-G-C	4	2.48e-6	-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.1335G>T	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is not reported in ClinVar (status: none) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized; those that agree on pathogenic include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Foldetta, and premPS. High‑accuracy methods give a split view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the predictions are inconclusive, with an equal number of benign and pathogenic calls. Thus, the variant is most likely benign based on the current evidence, 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.1354G>C	V452L 2D 3DClick to see structure in 3D Viewer AISynGAP1 V452L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. 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. Because the majority of tools (six) predict benign and the high‑accuracy Foldetta also supports benign, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-11.285	Likely Pathogenic	0.929	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	-0.25	Likely Benign	0.02	Likely Benign	0.34	Likely Benign	0.316	Likely Benign	-2.96	Deleterious	0.947	Possibly Damaging	0.851	Possibly Damaging	3.54	Benign	0.11	Tolerated			0.0777	0.4061		2	1	-0.4	14.03
c.2035T>C	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L 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 Rosetta, Foldetta, and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) 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 (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for F679L, 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	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.506	Likely Pathogenic	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>A	F679L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F679L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, FATHMM, and Foldetta, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. 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	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>G	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and premPS are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.4002C>A	N1334K 2D AIThe SynGAP1 missense variant N1334K is listed in gnomAD (ID 6‑33451876‑C‑A) but has no ClinVar record. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (2 pathogenic vs 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy methods do not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875								6-33451876-C-A			-4.875	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.109	Likely Benign	-3.49	Deleterious	0.979	Probably Damaging	0.756	Possibly Damaging	3.54	Benign	0.00	Affected	3.77	5	0.2355	0.5163		0	1	-0.4	14.07
c.4002C>G	N1334K 2D AIThe SynGAP1 missense variant N1334K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are limited: AlphaMissense‑Optimized remains inconclusive; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 tie and therefore unavailable; Foldetta predictions are not provided. Overall, the balance of evidence favors a pathogenic effect for N1334K. 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.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-4.875	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-3.49	Deleterious	0.979	Probably Damaging	0.756	Possibly Damaging	3.54	Benign	0.00	Affected	3.77	5	0.2355	0.5163		0	1	-0.4	14.07
c.422T>A	I141N 2D AIThe SynGAP1 missense variant I141N is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic. Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141N. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-12.417	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.258	Likely Benign	-3.90	Deleterious	0.799	Possibly Damaging	0.424	Benign	3.54	Benign	0.00	Affected			0.1047	0.0270		-2	-3	-8.0	0.94
c.554C>G	S185C 2D AIThe SynGAP1 missense variant S185C has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (derived from the same set of predictors) also reports likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.612	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.266	Likely Benign	-3.96	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.54	Benign	0.00	Affected			0.0989	0.6000		0	-1	3.3	16.06
c.1252A>C	K418Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K418Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-11.404	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.17	Likely Benign	0.14	Likely Benign	0.30	Likely Benign	0.263	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.55	Benign	0.13	Tolerated			0.4105	0.0696		1	1	0.4	-0.04
c.1349C>T	A450V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A450V is not reported in ClinVar and is present in gnomAD (ID 6‑33438254‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools lean toward a benign effect, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign based on current predictions, with a single high‑accuracy tool suggesting pathogenicity but not overturning the overall benign consensus. 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								6-33438254-C-T	1	6.20e-7	-11.489	Likely Pathogenic	0.578	Likely Pathogenic	Likely Benign	0.04	Likely Benign	0.2	0.27	Likely Benign	0.16	Likely Benign	0.46	Likely Benign	0.306	Likely Benign	-3.69	Deleterious	0.998	Probably Damaging	0.955	Probably Damaging	3.55	Benign	0.04	Affected	3.37	32	0.0792	0.5638		0	0	2.4	28.05
c.1443C>A	H481Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H481Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized classifies the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the balance of evidence leans toward a benign effect, 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	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.524	Likely Pathogenic	0.663	Likely Pathogenic	Likely Benign	-0.41	Likely Benign	0.1	0.31	Likely Benign	-0.05	Likely Benign	0.32	Likely Benign	0.243	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.55	Benign	0.51	Tolerated			0.1052	0.2797		3	0	-0.3	-9.01
c.1443C>G	H481Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H481Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized classifies the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the balance of evidence leans toward a benign effect, 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	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.524	Likely Pathogenic	0.663	Likely Pathogenic	Likely Benign	-0.41	Likely Benign	0.1	0.31	Likely Benign	-0.05	Likely Benign	0.32	Likely Benign	0.243	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.55	Benign	0.51	Tolerated			0.1052	0.2797		3	0	-0.3	-9.01
c.1932C>A	D644E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D644E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments confirm a benign impact: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-1.778	Likely Benign	0.178	Likely Benign	Likely Benign	-0.17	Likely Benign	0.1	-0.51	Ambiguous	-0.34	Likely Benign	-0.47	Likely Benign	0.132	Likely Benign	1.31	Neutral	0.000	Benign	0.000	Benign	3.55	Benign	1.00	Tolerated			0.1528	0.6186		3	2	0.0	14.03
c.1932C>G	D644E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D644E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments confirm a benign impact: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-1.778	Likely Benign	0.178	Likely Benign	Likely Benign	-0.17	Likely Benign	0.1	-0.51	Ambiguous	-0.34	Likely Benign	-0.47	Likely Benign	0.132	Likely Benign	1.31	Neutral	0.000	Benign	0.000	Benign	3.55	Benign	1.00	Tolerated			0.1528	0.6186		3	2	0.0	14.03
c.1940G>C	G647A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. Predictions that are inconclusive are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as Uncertain. Taken together, the overwhelming majority of evidence indicates a benign effect for G647A, 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	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-0.266	Likely Benign	0.078	Likely Benign	Likely Benign	-0.18	Likely Benign	0.0	-0.99	Ambiguous	-0.59	Ambiguous	-0.69	Ambiguous	0.037	Likely Benign	0.48	Neutral	0.000	Benign	0.002	Benign	3.55	Benign	0.81	Tolerated			0.3558	0.4136		1	0	2.2	14.03
c.1994A>C	Y665S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic, and Foldetta is uncertain (treated as unavailable). Overall, the balance of evidence, particularly the pathogenic signal from the SGM Consensus and the equal split among standard predictors, indicates that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-9.110	Likely Pathogenic	0.453	Ambiguous	Likely Benign	1.24	Ambiguous	0.2	1.40	Ambiguous	1.32	Ambiguous	0.87	Ambiguous	0.202	Likely Benign	-2.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.55	Benign	0.62	Tolerated			0.3995	0.1793		-3	-2	0.5	-76.10
c.2104C>G	Q702E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta give uncertain results. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign; Foldetta remains inconclusive. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.974	Likely Pathogenic	0.230	Likely Benign	Likely Benign	0.48	Likely Benign	0.0	0.72	Ambiguous	0.60	Ambiguous	0.27	Likely Benign	0.196	Likely Benign	-2.27	Neutral	0.989	Probably Damaging	0.930	Probably Damaging	3.55	Benign	0.15	Tolerated			0.1021	0.1609		2	2	0.0	0.98
c.2167A>T	T723S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The high‑accuracy consensus methods confirm the benign assessment: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the majority of evidence supports a benign impact for T723S, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-4.792	Likely Benign	0.091	Likely Benign	Likely Benign	-0.26	Likely Benign	0.0	0.28	Likely Benign	0.01	Likely Benign	0.23	Likely Benign	0.037	Likely Benign	-0.89	Neutral	0.673	Possibly Damaging	0.678	Possibly Damaging	3.55	Benign	0.06	Tolerated			0.3171	0.3731		1	1	-0.1	-14.03
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.4000A>G	N1334D 2D AIThe SynGAP1 missense variant N1334D (ClinVar ID 3653769.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33451874‑A‑G). Functional prediction tools show a split: benign calls come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, an inconclusive SGM Consensus (a 2‑vs‑2 majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no available Foldetta stability data. Overall, the majority of predictions (5/10) indicate pathogenicity, and the high‑accuracy tools do not overturn this trend. Therefore, the variant is most likely pathogenic, which does not contradict its ClinVar status of Uncertain. 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					Uncertain		1	6-33451874-A-G			-4.584	Likely Benign	0.674	Likely Pathogenic	Likely Benign										0.126	Likely Benign	-3.06	Deleterious	0.886	Possibly Damaging	0.522	Possibly Damaging	3.55	Benign	0.00	Affected	3.77	5	0.2444	0.3307		1	2	0.0	0.98
c.554C>T	S185F 2D AIThe SynGAP1 missense variant S185F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S185F. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-13.327	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.356	Likely Benign	-5.03	Deleterious	0.838	Possibly Damaging	0.466	Possibly Damaging	3.55	Benign	0.00	Affected			0.0628	0.5563		-3	-2	3.6	60.10
c.1427T>C	F476S 2D AIThe SynGAP1 missense variant F476S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields an equal split of pathogenic and benign signals. Overall, the balance of evidence favors a pathogenic effect for F476S, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-12.675	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	3.02	Destabilizing	0.9	4.07	Destabilizing	3.55	Destabilizing	1.23	Destabilizing	0.278	Likely Benign	-2.33	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.56	Benign	0.44	Tolerated			0.3387	0.0558		-3	-2	-3.6	-60.10
c.1978A>C	M660L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, 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. No predictions are missing or inconclusive. Overall, the balance of evidence leans toward a benign classification, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-12.576	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	0.16	Likely Benign	0.0	-0.10	Likely Benign	0.03	Likely Benign	0.97	Ambiguous	0.330	Likely Benign	-2.99	Deleterious	0.596	Possibly Damaging	0.101	Benign	3.56	Benign	0.03	Affected			0.1337	0.3891		4	2	1.9	-18.03
c.1978A>G	M660V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into three groups: benign predictions come from REVEL, SIFT, and FATHMM; pathogenic predictions arise from SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evaluated predictors lean toward a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status is available. Thus, based on the current computational evidence, the M660V variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.006	Likely Pathogenic	0.836	Likely Pathogenic	Ambiguous	1.83	Ambiguous	0.1	0.77	Ambiguous	1.30	Ambiguous	1.05	Destabilizing	0.419	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.927	Probably Damaging	3.56	Benign	0.13	Tolerated			0.2614	0.2937		2	1	2.3	-32.06
c.1978A>T	M660L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, 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. No predictions are missing or inconclusive. Overall, the balance of evidence leans 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 Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-12.576	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	0.16	Likely Benign	0.0	-0.10	Likely Benign	0.03	Likely Benign	0.97	Ambiguous	0.330	Likely Benign	-2.99	Deleterious	0.596	Possibly Damaging	0.101	Benign	3.56	Benign	0.03	Affected			0.1337	0.3891		4	2	1.9	-18.03
c.4001A>G	N1334S 2D AIThe SynGAP1 missense variant N1334S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign consensus (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-3.989	Likely Benign	0.409	Ambiguous	Likely Benign										0.107	Likely Benign	-2.94	Deleterious	0.557	Possibly Damaging	0.348	Benign	3.56	Benign	0.00	Affected			0.3542	0.4708		1	1	2.7	-27.03
c.413A>C	K138T 2D AIThe SynGAP1 missense variant K138T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, with no high‑accuracy consensus supporting pathogenicity. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-5.143	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-3.45	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.01	Affected			0.1940	0.2806		0	-1	3.2	-27.07
c.414A>C	K138N 2D AIThe SynGAP1 missense variant K138N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.414A>T	K138N 2D AIThe SynGAP1 missense variant K138N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.422T>G	I141S 2D AIThe SynGAP1 missense variant I141S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus also as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141S, 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	0.577021	Binding	0.367	0.877	0.500											-11.874	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.267	Likely Benign	-3.28	Deleterious	0.567	Possibly Damaging	0.249	Benign	3.56	Benign	0.00	Affected			0.2885	0.0840		-1	-2	-5.3	-26.08
c.446A>C	K149T 2D AIThe SynGAP1 missense variant K149T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic calls arise from 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 effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are unavailable, so no stability evidence is provided. 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		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-11.948	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.260	Likely Benign	-3.53	Deleterious	0.141	Benign	0.091	Benign	3.56	Benign	0.00	Affected			0.2398	0.3473		0	-1	3.2	-27.07
c.447A>C	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.447A>T	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for K149N, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.553T>C	S185P 2D AIThe SynGAP1 missense variant S185P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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 evidence from both general and high‑accuracy predictors indicates that the S185P 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		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-15.129	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-4.02	Deleterious	0.940	Possibly Damaging	0.462	Possibly Damaging	3.56	Benign	0.00	Affected			0.2156	0.5242		1	-1	-0.8	10.04
c.554C>A	S185Y 2D AIThe SynGAP1 missense variant S185Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-13.633	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.316	Likely Benign	-4.93	Deleterious	0.718	Possibly Damaging	0.178	Benign	3.56	Benign	0.00	Affected			0.0736	0.5439		-3	-2	-0.5	76.10
c.1561G>A	E521K 2D 3DClick to see structure in 3D Viewer AISynGAP1 E521K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. Overall, the majority of conventional tools lean toward a benign interpretation, while the high‑accuracy methods are split. Thus, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-9.596	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	-0.48	Likely Benign	0.2	0.14	Likely Benign	-0.17	Likely Benign	-0.10	Likely Benign	0.379	Likely Benign	-3.05	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	3.57	Benign	0.45	Tolerated			0.2895	0.6513		0	1	-0.4	-0.94
c.1936C>A	L646M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. Predictions that are inconclusive are FoldX, 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, while Foldetta’s stability analysis remains uncertain. Overall, the evidence overwhelmingly supports a benign classification for this variant, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-1.911	Likely Benign	0.152	Likely Benign	Likely Benign	0.70	Ambiguous	0.1	1.66	Ambiguous	1.18	Ambiguous	-1.10	Stabilizing	0.106	Likely Benign	1.86	Neutral	0.211	Benign	0.055	Benign	3.57	Benign	1.00	Tolerated			0.2041	0.3427		4	2	-1.9	18.03
c.2080G>T	A694S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The only inconclusive results come from Rosetta and premPS, which are listed as uncertain and do not influence the overall assessment. High‑accuracy predictors reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Consequently, the variant is most likely benign, and this prediction is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-0.326	Likely Benign	0.076	Likely Benign	Likely Benign	0.22	Likely Benign	0.1	0.59	Ambiguous	0.41	Likely Benign	-0.53	Ambiguous	0.092	Likely Benign	0.70	Neutral	0.013	Benign	0.021	Benign	3.57	Benign	1.00	Tolerated			0.2725	0.4231		1	1	-2.6	16.00
c.397C>A	L133M 2D AIThe SynGAP1 missense variant L133M is not 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, and AlphaMissense‑Default; ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta results are unavailable. Overall, the majority of standard predictors (four pathogenic vs. three benign) indicate a pathogenic 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.			0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-7.993	In-Between	0.841	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-0.77	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	3.57	Benign	0.03	Affected			0.0856	0.2229		4	2	-1.9	18.03
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.422T>C	I141T 2D AIThe SynGAP1 missense variant I141T 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. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious 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 reported result for this variant, so its contribution is unavailable. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-10.580	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.251	Likely Benign	-2.81	Deleterious	0.272	Benign	0.167	Benign	3.57	Benign	0.00	Affected			0.1165	0.1214		0	-1	-5.2	-12.05
c.423C>G	I141M 2D AIThe SynGAP1 I141M 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 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are mixed, with an equal split between benign and pathogenic calls and no definitive evidence from Foldetta. Thus, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-7.437	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.112	Likely Benign	-1.54	Neutral	0.567	Possibly Damaging	0.332	Benign	3.57	Benign	0.01	Affected			0.0664	0.2661		2	1	-2.6	18.03
c.1279C>G	H427D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H427D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No evidence from the available tools suggests pathogenicity, and the absence of a ClinVar classification means there is no contradiction. Therefore, based on the current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-3.684	Likely Benign	0.500	Ambiguous	Likely Benign	0.76	Ambiguous	0.1	1.26	Ambiguous	1.01	Ambiguous	0.10	Likely Benign	0.163	Likely Benign	-1.43	Neutral	0.677	Possibly Damaging	0.236	Benign	3.58	Benign	0.12	Tolerated			0.2241	0.1678		1	-1	-0.3	-22.05
c.1301T>C	V434A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V434A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; FoldX and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-8.531	Likely Pathogenic	0.441	Ambiguous	Likely Benign	1.72	Ambiguous	0.0	2.51	Destabilizing	2.12	Destabilizing	1.00	Destabilizing	0.238	Likely Benign	-2.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.75	Tolerated			0.2338	0.2292		0	0	-2.4	-28.05
c.1675T>A	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Based on the overall distribution of predictions, the variant is most likely pathogenic; this conclusion does not contradict the ClinVar status, which has no classification. 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											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.450	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.1676G>C	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: premPS (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta) as Benign, and AlphaMissense‑Optimized as Uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.469	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.1840T>C	Y614H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and Rosetta. Tools with uncertain or inconclusive results (FoldX, Foldetta, premPS) are not considered evidence for either side. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-9.678	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.17	Ambiguous	0.5	2.38	Destabilizing	1.78	Ambiguous	0.91	Ambiguous	0.397	Likely Benign	-4.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.58	Benign	0.27	Tolerated			0.1948	0.0373		0	2	-1.9	-26.03
c.1972G>A	G658S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658S is reported in gnomAD (variant ID 6-33441231‑G‑A) but has no entry in ClinVar. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, 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 only inconclusive result comes from Rosetta, which is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000								6-33441231-G-A	8	4.96e-6	-3.445	Likely Benign	0.077	Likely Benign	Likely Benign	-0.12	Likely Benign	0.0	-0.50	Ambiguous	-0.31	Likely Benign	-0.11	Likely Benign	0.070	Likely Benign	-0.97	Neutral	0.209	Benign	0.087	Benign	3.58	Benign	0.43	Tolerated	3.39	24	0.2783	0.3576		0	1	-0.4	30.03
c.2090G>T	W697L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697L 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, Foldetta, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No predictions are missing or inconclusive. Overall, the majority of tools (seven pathogenic vs. six benign) lean toward a pathogenic interpretation, and this 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	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-9.057	Likely Pathogenic	0.676	Likely Pathogenic	Likely Benign	0.20	Likely Benign	0.1	-0.17	Likely Benign	0.02	Likely Benign	0.90	Ambiguous	0.280	Likely Benign	-8.48	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	3.58	Benign	0.02	Affected			0.2222	0.2848		-2	-2	4.7	-73.05
c.412A>C	K138Q 2D AIThe SynGAP1 missense variant K138Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-8.122	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.173	Likely Benign	-2.15	Neutral	0.700	Possibly Damaging	0.310	Benign	3.58	Benign	0.01	Affected			0.4171	0.1272		1	1	0.4	-0.04
c.587T>G	L196W 2D AIThe SynGAP1 missense variant L196W has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD. 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, PROVEAN)—all predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for this variant, 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		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-12.148	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.293	Likely Benign	-4.91	Deleterious	0.992	Probably Damaging	0.869	Possibly Damaging	3.58	Benign	0.00	Affected			0.0551	0.2718		-2	-2	-4.7	73.05
c.1286G>T	R429L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. No contradictory evidence is present from ClinVar or gnomAD. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-6.495	Likely Benign	0.408	Ambiguous	Likely Benign	-0.05	Likely Benign	0.1	0.06	Likely Benign	0.01	Likely Benign	-0.12	Likely Benign	0.241	Likely Benign	-1.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.59	Benign	0.37	Tolerated			0.1555	0.4025		-3	-2	8.3	-43.03
c.1964T>A	L655Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655Q is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity, while Rosetta remains inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of evidence supports a benign impact for L655Q, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000					Uncertain		1				-5.278	Likely Benign	0.144	Likely Benign	Likely Benign	-0.01	Likely Benign	0.0	0.69	Ambiguous	0.34	Likely Benign	-0.15	Likely Benign	0.139	Likely Benign	0.61	Neutral	0.955	Possibly Damaging	0.602	Possibly Damaging	3.59	Benign	0.65	Tolerated	3.39	24	0.1248	0.0972		-2	-2	-7.3	14.97	229.9	-8.6	0.0	0.0	0.4	0.0						X		Potentially Benign	The iso-butyl side chain of Leu655, located on the surface of an α helix (res. Ser641-Glu666), is not involved in any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Gln655 dynamically interacts with neighboring residues (e.g., Glu651, Glu656, Arg544) on the protein surface, with no negative structural effects.
c.1981C>A	Q661K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Only ESM1b predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic, with one uncertain), and Foldetta also predicts benign stability. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-10.581	Likely Pathogenic	0.400	Ambiguous	Likely Benign	-0.01	Likely Benign	0.0	-0.18	Likely Benign	-0.10	Likely Benign	0.04	Likely Benign	0.108	Likely Benign	-1.89	Neutral	0.098	Benign	0.030	Benign	3.59	Benign	0.42	Tolerated			0.1756	0.3592		1	1	-0.4	0.04
c.2035T>A	F679I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM. In contrast, a majority of predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently classify the substitution as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as Likely Pathogenic. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains pathogenic. Because the uncertain results are treated as unavailable, the clear majority of predictions support pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for F679I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-12.620	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.62	Ambiguous	0.4	-0.27	Likely Benign	0.68	Ambiguous	0.88	Ambiguous	0.498	Likely Benign	-5.91	Deleterious	0.993	Probably Damaging	0.977	Probably Damaging	3.59	Benign	0.01	Affected			0.1725	0.2322		1	0	1.7	-34.02
c.326G>C	S109T 2D AIThe SynGAP1 missense variant S109T is catalogued in gnomAD (6‑33432191‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all report benign or likely benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments confirm the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus, derived from the majority of the high‑accuracy predictors, is benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S109T is most likely benign, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750								6-33432191-G-C	2	1.24e-6	-4.065	Likely Benign	0.449	Ambiguous	Likely Benign										0.090	Likely Benign	-1.19	Neutral	0.231	Benign	0.050	Benign	3.59	Benign	0.00	Affected	3.61	5	0.1519	0.5212		1	1	0.1	14.03
c.3991A>G	I1331V 2D AIThe SynGAP1 missense variant I1331V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Benign,” and Foldetta 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		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-2.799	Likely Benign	0.899	Likely Pathogenic	Ambiguous										0.138	Likely Benign	-0.51	Neutral	0.581	Possibly Damaging	0.785	Possibly Damaging	3.59	Benign	0.00	Affected			0.1091	0.3074		4	3	-0.3	-14.03
c.4001A>C	N1334T 2D AIThe SynGAP1 missense variant N1334T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, which evaluates protein‑folding stability, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-4.249	Likely Benign	0.576	Likely Pathogenic	Likely Benign										0.103	Likely Benign	-3.45	Deleterious	0.047	Benign	0.063	Benign	3.59	Benign	0.00	Affected			0.1600	0.5519		0	0	2.8	-13.00
c.410T>C	L137P 2D AIThe SynGAP1 missense variant L137P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of 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 indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). 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											-11.067	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.377	Likely Benign	-3.77	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.59	Benign	0.00	Affected			0.3620	0.1177		-3	-3	-5.4	-16.04
c.418T>A	S140T 2D AIThe SynGAP1 missense variant S140T is not reported 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, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) remains Likely Benign. Foldetta predictions are unavailable. Overall, the balance of evidence, particularly the SGM‑Consensus and the majority of benign‑predicting tools, suggests that the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-6.336	Likely Benign	0.873	Likely Pathogenic	Ambiguous										0.132	Likely Benign	-1.94	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.59	Benign	0.03	Affected			0.1069	0.5722		1	1	0.1	14.03
c.434A>T	K145M 2D AIThe SynGAP1 missense variant K145M 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, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K145M 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		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-9.884	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.245	Likely Benign	-3.47	Deleterious	0.964	Probably Damaging	0.650	Possibly Damaging	3.59	Benign	0.00	Affected			0.1041	0.4427		0	-1	5.8	3.02
c.445A>G	K149E 2D AIThe SynGAP1 missense variant K149E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields an equal split (2 vs 2) and is therefore considered unavailable. AlphaMissense‑Optimized, a high‑accuracy predictor, classifies the variant as pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-12.148	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.231	Likely Benign	-2.17	Neutral	0.141	Benign	0.062	Benign	3.59	Benign	0.00	Affected			0.4636	0.1022		0	1	0.4	0.94
c.69T>A	D23E 2D AIThe SynGAP1 D23E 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 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 unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-3.329	Likely Benign	0.565	Likely Pathogenic	Likely Benign										0.084	Likely Benign	-1.35	Neutral	0.643	Possibly Damaging	0.417	Benign	3.59	Benign	0.00	Affected	4.32	1	0.2420	0.8363		2	3	0.0	14.03
c.69T>G	D23E 2D AIThe SynGAP1 missense variant D23E is listed in gnomAD (ID 6‑33423478‑T‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence—including the consensus and high‑accuracy tools—points to a benign effect, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375								6-33423478-T-G	15	9.29e-6	-3.329	Likely Benign	0.565	Likely Pathogenic	Likely Benign										0.084	Likely Benign	-1.35	Neutral	0.643	Possibly Damaging	0.417	Benign	3.59	Benign	0.00	Affected	4.32	1	0.2420	0.8363		2	3	0.0	14.03
c.1772C>G	A591G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only PROVEAN predicts a pathogenic outcome. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for A591G, 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	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000											-6.596	Likely Benign	0.233	Likely Benign	Likely Benign	1.22	Ambiguous	0.2	1.74	Ambiguous	1.48	Ambiguous	0.83	Ambiguous	0.142	Likely Benign	-2.77	Deleterious	0.007	Benign	0.009	Benign	3.60	Benign	0.16	Tolerated			0.2117	0.2228		1	0	-2.2	-14.03
c.1906T>C	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by 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, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus confirms Likely Pathogenic, and the Foldetta stability analysis is inconclusive. Other stability tools (FoldX, Rosetta, premPS) are uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy methods, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.478	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1908T>A	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by 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, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus confirms Likely Pathogenic, and the Foldetta stability analysis is inconclusive. Other stability tools (FoldX, Rosetta, premPS) are uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy methods, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.268	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1908T>G	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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 effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from FoldX‑MD, Rosetta, or premPS is available to alter this view. Overall, the majority of reliable predictors indicate a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.268	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1918A>T	T640S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640S is listed in ClinVar as Benign (ClinVar ID 2980241.0) and is present in the gnomAD database (gnomAD ID 6‑33441177‑A‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive result is from FoldX, which is treated as unavailable. High‑accuracy assessments confirm benignity: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Overall, the variant is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000					Benign		1	6-33441177-A-T	1	6.20e-7	-2.371	Likely Benign	0.062	Likely Benign	Likely Benign	-0.78	Ambiguous	0.1	0.43	Likely Benign	-0.18	Likely Benign	-0.30	Likely Benign	0.088	Likely Benign	0.92	Neutral	0.000	Benign	0.001	Benign	3.60	Benign	0.33	Tolerated	3.37	30	0.3406	0.3484		1	1	-0.1	-14.03
c.1919C>G	T640S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, premPS, Foldetta, Rosetta, REVEL, and the SGM‑Consensus score (Likely Benign) all classify the change as tolerated. No tool predicts pathogenicity; the only inconclusive result is from FoldX, which is listed as Uncertain. High‑accuracy methods corroborate the benign assessment: AlphaMissense‑Optimized predicts Benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Benign. Consequently, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-2.371	Likely Benign	0.062	Likely Benign	Likely Benign	-0.78	Ambiguous	0.1	0.43	Likely Benign	-0.18	Likely Benign	-0.30	Likely Benign	0.109	Likely Benign	0.92	Neutral	0.000	Benign	0.001	Benign	3.60	Benign	0.33	Tolerated	3.37	30	0.3406	0.3484		1	1	-0.1	-14.03
c.2189T>G	I730S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all uniformly predict a benign impact. Based on the collective evidence, the variant is most likely benign, 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		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-6.220	Likely Benign	0.349	Ambiguous	Likely Benign	0.25	Likely Benign	0.2	-0.12	Likely Benign	0.07	Likely Benign	0.47	Likely Benign	0.123	Likely Benign	-0.51	Neutral	1.000	Probably Damaging	0.967	Probably Damaging	3.60	Benign	0.34	Tolerated			0.2646	0.0903		-1	-2	-5.3	-26.08
c.3358G>C	G1120R 2D AIThe SynGAP1 missense variant G1120R is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact for G1120R, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875											-8.784	Likely Pathogenic	0.565	Likely Pathogenic	Likely Benign										0.333	Likely Benign	-0.77	Neutral	0.666	Possibly Damaging	0.221	Benign	3.60	Benign	0.05	Affected			0.0994	0.4142		-3	-2	-4.1	99.14
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.3359G>A	G1120D 2D AIThe SynGAP1 missense variant G1120D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443911‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is 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.			0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875								6-33443911-G-A	4	2.65e-6	-9.244	Likely Pathogenic	0.378	Ambiguous	Likely Benign										0.351	Likely Benign	-0.82	Neutral	0.666	Possibly Damaging	0.355	Benign	3.60	Benign	0.19	Tolerated	3.77	5	0.1659	0.1835		-1	1	-3.1	58.04
c.410T>A	L137Q 2D AIThe SynGAP1 missense variant L137Q 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. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-12.246	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.356	Likely Benign	-3.43	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.60	Benign	0.00	Affected			0.1137	0.1049		-2	-2	-7.3	14.97
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.412A>G	K138E 2D AIThe SynGAP1 missense variant K138E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). AlphaMissense‑Optimized specifically predicts pathogenicity, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of predictions lean toward a benign outcome (5 benign vs 4 pathogenic), and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-11.902	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.212	Likely Benign	-2.13	Neutral	0.247	Benign	0.125	Benign	3.60	Benign	0.01	Affected			0.3611	0.0974		0	1	0.4	0.94
c.436T>C	S146P 2D AIThe SynGAP1 missense variant S146P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S146P, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-13.292	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-3.11	Deleterious	0.392	Benign	0.230	Benign	3.60	Benign	0.00	Affected			0.1934	0.4627		1	-1	-0.8	10.04
c.553T>A	S185T 2D AIThe SynGAP1 missense variant S185T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a pathogenic impact. The variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.943	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-2.54	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.60	Benign	0.00	Affected			0.1484	0.6236		1	1	0.1	14.03
c.556T>G	L186V 2D AIThe SynGAP1 missense variant L186V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are also unavailable. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-9.385	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic										0.090	Likely Benign	-2.27	Neutral	0.734	Possibly Damaging	0.185	Benign	3.60	Benign	0.00	Affected			0.1419	0.3665		2	1	0.4	-14.03
c.1213C>T	R405C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R405C is listed in ClinVar with an uncertain significance (ClinVar ID 1185858.0) and is present in gnomAD (ID 6‑33438118‑C‑T). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise premPS, 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 a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. FoldX and Rosetta individually return uncertain results. Overall, the balance of evidence favors a pathogenic interpretation, which does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000					Conflicting		2	6-33438118-C-T	6	3.72e-6	-9.206	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	0.72	Ambiguous	0.1	1.51	Ambiguous	1.12	Ambiguous	1.21	Destabilizing	0.427	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.61	Benign	0.02	Affected	3.38	28	0.3227	0.3964		-4	-3	7.0	-53.05	221.3	82.6	-0.1	0.0	-0.2	0.3	X	X						Potentially Pathogenic	The guanidinium group of Arg405, located in an anti-parallel β sheet strand of the C2 domain (res. Ala399-Ile411), forms a salt bridge with the carboxylate group of the Glu446 side chain from an opposing α helix (res. Val441-Ser457) in the GAP domain. The positively charged Arg405 side chain also stacks with the aromatic ring of the Phe358 side chain from a loop preceding the β strand (res. Thr359-Thr366), which could assist in maintaining the anti-parallel strand arrangement.In the variant simulations, the thiol-containing side chain of Cys405 is neutral and smaller compared to the arginine side chain. The lack of Arg405-Phe358 stacking affects the loop structure, causing it to assume a β strand form—an effect that could be exacerbated during protein folding. Moreover, the inability of Cys405 to form a salt bridge with Glu446 could affect the tertiary structure assembly, although this is not apparent based on the variant simulations.
c.1339G>C	V447L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V447L is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Uncertain results are reported by FoldX, Rosetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Benign. Overall, the majority of evidence points to a benign effect, and this consensus does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000					Uncertain		1				-5.136	Likely Benign	0.491	Ambiguous	Likely Benign	-1.13	Ambiguous	0.1	0.54	Ambiguous	-0.30	Likely Benign	0.03	Likely Benign	0.180	Likely Benign	-0.29	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.61	Benign	0.90	Tolerated	3.37	32	0.0757	0.3477		1	2	-0.4	14.03
c.1934T>A	F645Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645Y 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, Rosetta, 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). Tools with inconclusive results are FoldX (Uncertain) and premPS (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized predicting Benign, the SGM‑Consensus indicating Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicting Benign. No tool predicts pathogenicity. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as the variant is not currently classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-3.544	Likely Benign	0.131	Likely Benign	Likely Benign	0.52	Ambiguous	0.2	0.21	Likely Benign	0.37	Likely Benign	-0.61	Ambiguous	0.141	Likely Benign	2.40	Neutral	0.000	Benign	0.000	Benign	3.61	Benign	1.00	Tolerated			0.1506	0.2189		7	3	-4.1	16.00
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.397C>G	L133V 2D AIThe SynGAP1 missense variant L133V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are limited: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes); Foldetta results are unavailable. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-8.429	Likely Pathogenic	0.848	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-1.27	Neutral	0.247	Benign	0.163	Benign	3.61	Benign	0.03	Affected			0.1561	0.1883		2	1	0.4	-14.03
c.445A>C	K149Q 2D AIThe SynGAP1 missense variant K149Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-11.430	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.99	Neutral	0.535	Possibly Damaging	0.310	Benign	3.61	Benign	0.00	Affected			0.5243	0.1454	Weaken	1	1	0.4	-0.04
c.1214G>C	R405P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates it is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies it as pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000					Uncertain		1				-14.206	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.3	5.19	Destabilizing	4.15	Destabilizing	1.26	Destabilizing	0.572	Likely Pathogenic	-6.32	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.62	Benign	0.01	Affected	3.38	28	0.2140	0.5138		-2	0	2.9	-59.07
c.1279C>A	H427N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign outcome. With all available evidence pointing to a neutral effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											1.162	Likely Benign	0.045	Likely Benign	Likely Benign	-0.11	Likely Benign	0.1	0.39	Likely Benign	0.14	Likely Benign	-0.48	Likely Benign	0.100	Likely Benign	1.63	Neutral	0.010	Benign	0.006	Benign	3.62	Benign	0.46	Tolerated			0.1507	0.2418		2	1	-0.3	-23.04
c.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.316A>T	R106W 2D AIThe SynGAP1 missense variant R106W is not 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, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (5) than benign (3), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-5.350	Likely Benign	0.875	Likely Pathogenic	Ambiguous										0.240	Likely Benign	-3.31	Deleterious	0.983	Probably Damaging	0.624	Possibly Damaging	3.62	Benign	0.00	Affected			0.1369	0.3995		2	-3	3.6	30.03
c.3977C>A	P1326Q 2D AIThe SynGAP1 missense variant P1326Q is listed in ClinVar (ID 2806103.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33451851‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875					Uncertain		1	6-33451851-C-A	1	6.40e-7	-5.422	Likely Benign	0.128	Likely Benign	Likely Benign										0.138	Likely Benign	-0.86	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	3.62	Benign	0.00	Affected	3.77	5	0.1769	0.4457		-1	0	-1.9	31.01
c.3977C>G	P1326R 2D AIThe SynGAP1 missense variant P1326R is listed in ClinVar (ID 2429486.0) 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 show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875					Uncertain		1				-5.097	Likely Benign	0.240	Likely Benign	Likely Benign										0.133	Likely Benign	-0.82	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	3.62	Benign	0.00	Affected	3.77	5	0.1710	0.2808		0	-2	-2.9	59.07
c.3977C>T	P1326L 2D AIThe SynGAP1 missense variant P1326L is listed in ClinVar (ID 1004879.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as “Likely Benign,” and AlphaMissense‑Optimized also predicts benign. No Foldetta (FoldX‑MD/ Rosetta) stability result is available for this variant. Overall, the majority of evidence—including the high‑confidence SGM consensus and AlphaMissense‑Optimized prediction—supports a benign classification, which 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		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875					Uncertain		1				-5.541	Likely Benign	0.115	Likely Benign	Likely Benign										0.117	Likely Benign	-1.06	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	3.62	Benign	0.00	Affected	3.77	5	0.2723	0.6113		-3	-3	5.4	16.04
c.418T>G	S140A 2D AIThe SynGAP1 missense variant S140A is not 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 AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. three benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-9.068	Likely Pathogenic	0.805	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-1.83	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.62	Benign	0.05	Affected			0.4449	0.4320		1	1	2.6	-16.00
c.617T>A	I206N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I206N is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL and FATHMM, while the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: 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 stability predictions, is pathogenic. No prediction or folding result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, 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	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-15.211	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.98	Destabilizing	0.2	2.57	Destabilizing	2.78	Destabilizing	2.04	Destabilizing	0.334	Likely Benign	-5.55	Deleterious	0.940	Possibly Damaging	0.641	Possibly Damaging	3.62	Benign	0.00	Affected			0.0689	0.0340		-2	-3	-8.0	0.94
c.1213C>G	R405G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405G 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 (combining FoldX‑MD and Rosetta outputs) is pathogenic. 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	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.836	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	3.22	Destabilizing	0.5	3.26	Destabilizing	3.24	Destabilizing	1.38	Destabilizing	0.419	Likely Benign	-6.35	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.63	Benign	0.01	Affected			0.3381	0.4139		-3	-2	4.1	-99.14
c.1240A>C	M414L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. Uncertain predictions come from premPS and ESM1b. 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 verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the preponderance of evidence indicates that M414L is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-7.980	In-Between	0.779	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	0.64	Ambiguous	0.336	Likely Benign	-2.40	Neutral	0.559	Possibly Damaging	0.495	Possibly Damaging	3.63	Benign	0.90	Tolerated			0.1323	0.4236		4	2	1.9	-18.03
c.1240A>T	M414L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. Uncertain predictions come from premPS and ESM1b. 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 verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the preponderance of evidence indicates that M414L is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-7.980	In-Between	0.779	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	0.64	Ambiguous	0.336	Likely Benign	-2.40	Neutral	0.559	Possibly Damaging	0.495	Possibly Damaging	3.63	Benign	0.90	Tolerated			0.1323	0.4236		4	2	1.9	-18.03
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.434A>C	K145T 2D AIThe SynGAP1 missense variant K145T is not reported in ClinVar and is absent from gnomAD. Computational assessment shows a split: benign predictions from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, whereas pathogenic predictions come from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, classifies the change as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus itself is a high‑confidence prediction; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K145T. Thus, the variant is most likely pathogenic, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.519	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.224	Likely Benign	-3.54	Deleterious	0.247	Benign	0.166	Benign	3.63	Benign	0.00	Affected			0.1965	0.3611		0	-1	3.2	-27.07
c.437C>T	S146L 2D AIThe SynGAP1 missense variant S146L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) which classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the majority of predictions indicate 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		0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-15.179	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.130	Likely Benign	-3.77	Deleterious	0.084	Benign	0.063	Benign	3.63	Benign	0.00	Affected			0.0856	0.4975		-3	-2	4.6	26.08
c.545C>G	S182C 2D AIThe SynGAP1 missense variant S182C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-12.707	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-3.14	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.63	Benign	0.00	Affected			0.1179	0.5800		0	-1	3.3	16.06
c.617T>G	I206S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I206S missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and polyPhen‑2 HumVar. All other evaluated algorithms (SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is pathogenic. Based on the preponderance of evidence from these tools, 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	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-13.711	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.73	Destabilizing	0.3	3.89	Destabilizing	3.81	Destabilizing	1.74	Destabilizing	0.251	Likely Benign	-4.86	Deleterious	0.838	Possibly Damaging	0.368	Benign	3.63	Benign	0.00	Affected			0.2189	0.0728		-1	-2	-5.3	-26.08
c.1214G>T	R405L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R405L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect 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) indicate a pathogenic or likely pathogenic impact. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta providing an inconclusive stability prediction. Overall, the preponderance of evidence points to a pathogenic effect for R405L, 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	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.576	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.43	Ambiguous	0.7	0.40	Likely Benign	0.92	Ambiguous	0.72	Ambiguous	0.512	Likely Pathogenic	-6.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.64	Benign	0.01	Affected			0.2126	0.5555		-3	-2	8.3	-43.03
c.1300G>C	V434L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools, Rosetta and AlphaMissense‑Default, give uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta, a protein‑folding stability method, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V434L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-8.697	Likely Pathogenic	0.477	Ambiguous	Likely Benign	-0.05	Likely Benign	0.0	1.02	Ambiguous	0.49	Likely Benign	0.20	Likely Benign	0.225	Likely Benign	-2.30	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.64	Benign	0.27	Tolerated			0.0895	0.3813		2	1	-0.4	14.03
c.245T>C	L82P 2D AIThe SynGAP1 missense variant L82P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33425853‑T‑C). 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, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375								6-33425853-T-C	1	6.20e-7	-7.667	In-Between	0.991	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.73	Deleterious	0.939	Possibly Damaging	0.162	Benign	3.64	Benign	0.00	Affected	4.32	1	0.3477	0.1118		-3	-3	-5.4	-16.04
c.317G>T	R106M 2D AIThe SynGAP1 missense variant R106M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Because the majority of tools (five of nine) predict pathogenicity and the most accurate predictor (AlphaMissense‑Optimized) also indicates pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-4.804	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.184	Likely Benign	-2.65	Deleterious	0.940	Possibly Damaging	0.360	Benign	3.64	Benign	0.00	Affected			0.1971	0.4146		0	-1	6.4	-24.99
c.3359G>C	G1120A 2D AIThe SynGAP1 missense variant G1120A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta results are unavailable. Overall, the consensus of available predictions indicates that G1120A is most likely benign, and this conclusion does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875											-7.192	In-Between	0.082	Likely Benign	Likely Benign										0.243	Likely Benign	-0.39	Neutral	0.264	Benign	0.139	Benign	3.64	Benign	0.28	Tolerated			0.3435	0.4944		1	0	2.2	14.03
c.449T>A	L150H 2D AIThe SynGAP1 missense variant L150H is not 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 high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized alone also predicts 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 independent predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-14.892	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-4.09	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	3.64	Benign	0.00	Affected			0.1011	0.0519		-2	-3	-7.0	23.98
c.449T>C	L150P 2D AIThe SynGAP1 missense variant L150P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of 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 indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). 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											-12.881	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-3.90	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.64	Benign	0.00	Affected			0.3557	0.1543		-3	-3	-5.4	-16.04
c.545C>A	S182Y 2D AIThe SynGAP1 missense variant S182Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while benign calls are made only by REVEL and FATHMM. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized indicates a pathogenic effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. A protein‑folding stability analysis with Foldetta is unavailable, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-15.951	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-4.40	Deleterious	0.940	Possibly Damaging	0.564	Possibly Damaging	3.64	Benign	0.00	Affected			0.0656	0.5158		-3	-2	-0.5	76.10
c.545C>T	S182F 2D AIThe SynGAP1 missense variant S182F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic, and the Foldetta stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the corroborating high‑accuracy tools, the variant is most likely pathogenic, with no conflict with ClinVar status (which is absent). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-12.027	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-4.30	Deleterious	0.838	Possibly Damaging	0.466	Possibly Damaging	3.64	Benign	0.00	Affected			0.0597	0.5482		-3	-2	3.6	60.10
c.586T>A	L196M 2D AIThe SynGAP1 missense variant L196M is not 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 predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result. Overall, more tools predict pathogenicity (5) than benignity (3), and the high‑accuracy predictions do not overturn this trend. Therefore, 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.			0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-8.957	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous										0.094	Likely Benign	-1.48	Neutral	0.971	Probably Damaging	0.691	Possibly Damaging	3.64	Benign	0.01	Affected			0.0689	0.2786		4	2	-1.9	18.03
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.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.618C>G	I206M 2D AIThe SynGAP1 I206M 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, and FATHMM, whereas tools that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With six pathogenic predictions versus four benign and three uncertain, the overall evidence leans toward pathogenicity. 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.		PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-10.008	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	0.42	Likely Benign	0.6	1.21	Ambiguous	0.82	Ambiguous	1.08	Destabilizing	0.085	Likely Benign	-2.42	Neutral	0.838	Possibly Damaging	0.467	Possibly Damaging	3.64	Benign	0.01	Affected			0.0576	0.2716		2	1	-2.6	18.03
c.1214G>A	R405H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R405H is listed in ClinVar with an uncertain significance (ClinVar ID 863440.0) and is present in gnomAD (variant ID 6‑33438119‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized reports a benign change, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenicity. Overall, the preponderance of evidence indicates that R405H is most likely pathogenic, which does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000					Conflicting		2	6-33438119-G-A	4	2.48e-6	-9.081	Likely Pathogenic	0.706	Likely Pathogenic	Likely Benign	2.79	Destabilizing	0.6	1.85	Ambiguous	2.32	Destabilizing	1.26	Destabilizing	0.371	Likely Benign	-4.54	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	3.65	Benign	0.01	Affected	3.38	28	0.3395	0.2363		2	0	1.3	-19.05	214.0	102.2	-0.1	0.0	-0.7	0.1		X						Potentially Pathogenic	The guanidinium group of Arg405, located in an anti-parallel β sheet strand of the C2 domain (res. Pro398-Ile411), forms a salt bridge with the carboxylate group of the Glu446 side chain from an opposing α helix (res. Val441-Ser457) in the GAP domain. The positively charged Arg405 side chain also stacks with the aromatic ring of the Phe358 side chain from a loop preceding the β strand (res. Thr359-Thr366), which could assist in maintaining the anti-parallel strand arrangement.In the variant simulations, the imidazole ring of His405 does not stack with the aromatic ring of Phe358 nor form any lasting H-bonds with the loop residues. The imidazole ring of His405 (neutral and epsilon protonated in the simulations) is unable to form a salt bridge with Glu446, which could affect the tertiary structure assembly, although this is not apparent based on the variant simulations.
c.316A>G	R106G 2D AIThe SynGAP1 missense variant R106G is listed in gnomAD (ID 6‑33432181‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 majority of evidence points to a benign impact. There is no ClinVar classification to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875								6-33432181-A-G	1	6.20e-7	-2.617	Likely Benign	0.835	Likely Pathogenic	Ambiguous										0.161	Likely Benign	-2.21	Neutral	0.421	Benign	0.050	Benign	3.65	Benign	0.00	Affected	4.05	3	0.3680	0.3980		-2	-3	4.1	-99.14
c.425A>G	K142R 2D AIThe SynGAP1 missense variant K142R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors benign (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-9.327	Likely Pathogenic	0.361	Ambiguous	Likely Benign										0.157	Likely Benign	-1.87	Neutral	0.399	Benign	0.212	Benign	3.65	Benign	0.00	Affected			0.4459	0.0858		3	2	-0.6	28.01
c.433A>C	K145Q 2D AIThe SynGAP1 missense variant K145Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy tools give no definitive verdict: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic according to current predictions, and there is no ClinVar annotation to contradict this ambiguous computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-9.676	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-2.34	Neutral	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.4233	0.1478		1	1	0.4	-0.04
c.435G>C	K145N 2D AIThe SynGAP1 missense variant K145N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for K145N, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
c.435G>T	K145N 2D AIThe SynGAP1 missense variant K145N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL (score 0.45), polyPhen‑2 HumVar (benign), and FATHMM (benign). Pathogenic predictions arise from PROVEAN (deleterious), polyPhen‑2 HumDiv (probably damaging), SIFT (deleterious), ESM1b (damaging), AlphaMissense‑Default (pathogenic), and AlphaMissense‑Optimized (pathogenic). The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
c.436T>A	S146T 2D AIThe SynGAP1 missense variant S146T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a tie (two pathogenic, two benign) and thus unavailable; Foldetta results are not provided. Overall, the majority of evidence (five benign vs. three pathogenic) 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.			0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-9.795	Likely Pathogenic	0.786	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-2.09	Neutral	0.084	Benign	0.042	Benign	3.65	Benign	0.00	Affected			0.1267	0.5075		1	1	0.1	14.03
c.553T>G	S185A 2D AIThe SynGAP1 missense variant S185A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. High‑accuracy assessments therefore show a likely pathogenic consensus from SGM‑Consensus, with no contradictory evidence from ClinVar or population databases. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-11.839	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-2.57	Deleterious	0.231	Benign	0.107	Benign	3.65	Benign	0.00	Affected			0.5147	0.4472	Weaken	1	1	2.6	-16.00
c.587T>C	L196S 2D AIThe SynGAP1 missense variant L196S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, while Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-9.987	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.353	Likely Benign	-4.75	Deleterious	0.437	Benign	0.186	Benign	3.65	Benign	0.00	Affected			0.3473	0.0736		-3	-2	-4.6	-26.08
c.617T>C	I206T 2D AIThe SynGAP1 I206T missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give consistent results: 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 overall evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not currently listed. 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											-10.812	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	2.43	Destabilizing	0.5	2.68	Destabilizing	2.56	Destabilizing	1.94	Destabilizing	0.252	Likely Benign	-3.78	Deleterious	0.421	Benign	0.156	Benign	3.65	Benign	0.00	Affected			0.0830	0.0669		0	-1	-5.2	-12.05
c.626T>A	V209E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V209E is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) all predict a pathogenic outcome. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, V209E 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	PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125											-14.366	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.53	Destabilizing	1.3	2.35	Destabilizing	2.94	Destabilizing	1.52	Destabilizing	0.403	Likely Benign	-4.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.65	Benign	0.00	Affected			0.0826	0.1652		-2	-2	-7.7	29.98
c.626T>G	V209G 2D AIThe SynGAP1 missense variant V209G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools (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) also yields a pathogenic classification; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. Taken together, the overwhelming majority of computational evidence indicates that V209G 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.		PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125											-13.763	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.05	Destabilizing	0.5	3.99	Destabilizing	3.52	Destabilizing	1.27	Destabilizing	0.390	Likely Benign	-5.49	Deleterious	0.829	Possibly Damaging	0.995	Probably Damaging	3.65	Benign	0.04	Affected			0.1600	0.2035		-1	-3	-4.6	-42.08
c.2040G>C	E680D 2D AIThe SynGAP1 missense variant E680D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-5.019	Likely Benign	0.289	Likely Benign	Likely Benign	0.21	Likely Benign	0.8	0.27	Likely Benign	0.24	Likely Benign	-0.10	Likely Benign	0.121	Likely Benign	-0.64	Neutral	0.906	Possibly Damaging	0.295	Benign	3.66	Benign	0.32	Tolerated			0.2199	0.5208		3	2	0.0	-14.03
c.2040G>T	E680D 2D AIThe SynGAP1 missense variant E680D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or likely benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, representing the sole discordant prediction. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding‑stability result is missing or inconclusive. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-5.019	Likely Benign	0.289	Likely Benign	Likely Benign	0.21	Likely Benign	0.8	0.27	Likely Benign	0.24	Likely Benign	-0.10	Likely Benign	0.121	Likely Benign	-0.64	Neutral	0.906	Possibly Damaging	0.295	Benign	3.66	Benign	0.32	Tolerated			0.2199	0.5208		3	2	0.0	-14.03
c.250C>T	R84C 2D AIThe SynGAP1 missense variant R84C is not 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 score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R84C 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		0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-9.044	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.243	Likely Benign	-3.25	Deleterious	0.999	Probably Damaging	0.876	Possibly Damaging	3.66	Benign	0.00	Affected			0.3281	0.3657		-4	-3	7.0	-53.05
c.413A>G	K138R 2D AIThe SynGAP1 missense variant K138R 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 K138R, and this conclusion does not conflict with the absence of a ClinVar assertion. The variant is most likely benign, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-5.135	Likely Benign	0.406	Ambiguous	Likely Benign										0.115	Likely Benign	-1.58	Neutral	0.247	Benign	0.163	Benign	3.66	Benign	0.02	Affected			0.4555	0.1036		3	2	-0.6	28.01
c.1213C>A	R405S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405S 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 pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts Pathogenic. Taken together, the overwhelming majority of evidence indicates that R405S is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.326	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.66	Destabilizing	0.5	2.08	Destabilizing	2.37	Destabilizing	1.22	Destabilizing	0.405	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.05	Affected			0.2829	0.4646		0	-1	3.7	-69.11
c.1310C>T	P437L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta are uncertain. Taken together, the majority of evidence points toward a pathogenic impact for P437L, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.554	Likely Pathogenic	0.787	Likely Pathogenic	Ambiguous	1.10	Ambiguous	0.0	-3.52	Stabilizing	-1.21	Ambiguous	0.35	Likely Benign	0.324	Likely Benign	-8.48	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.67	Benign	0.04	Affected			0.2228	0.6354		-3	-3	5.4	16.04
c.2008C>G	L670V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L670V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign. Only ESM1b predicts pathogenicity, while FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a benign interpretation, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.829	Likely Pathogenic	0.113	Likely Benign	Likely Benign	1.45	Ambiguous	0.1	1.05	Ambiguous	1.25	Ambiguous	0.15	Likely Benign	0.025	Likely Benign	-0.60	Neutral	0.127	Benign	0.023	Benign	3.67	Benign	0.74	Tolerated			0.1558	0.4108		2	1	0.4	-14.03
c.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.244C>A	L82M 2D AIThe SynGAP1 missense variant L82M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized prediction is uncertain, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-4.608	Likely Benign	0.888	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-0.68	Neutral	0.939	Possibly Damaging	0.114	Benign	3.67	Benign	0.00	Affected			0.0744	0.3278		4	2	-1.9	18.03
c.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.251G>C	R84P 2D AIThe SynGAP1 missense variant R84P 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 remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b is uncertain and does not influence the consensus. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R84P 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.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-7.959	In-Between	0.994	Likely Pathogenic	Likely Pathogenic										0.157	Likely Benign	-2.50	Deleterious	0.989	Probably Damaging	0.859	Possibly Damaging	3.67	Benign	0.00	Affected			0.1978	0.4231		0	-2	2.9	-59.07
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.317G>C	R106T 2D AIThe SynGAP1 missense variant R106T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Separately, the high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while AlphaMissense‑Optimized remains uncertain and Foldetta data are missing. Based on the overall pattern of 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		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-4.197	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.229	Likely Benign	-2.30	Neutral	0.004	Benign	0.002	Benign	3.67	Benign	0.00	Affected			0.1941	0.4742		-1	-1	3.8	-55.08
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.544T>C	S182P 2D AIThe SynGAP1 missense variant S182P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates 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 independent predictors 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		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-13.362	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.279	Likely Benign	-3.71	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.67	Benign	0.00	Affected			0.2438	0.5030		1	-1	-0.8	10.04
c.1205T>C	L402P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L402P is not reported in ClinVar and is absent from gnomAD. Consensus among in‑silico predictors is overwhelmingly pathogenic: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a deleterious effect, whereas only FATHMM predicts a benign outcome. High‑accuracy tools 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 effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the evidence strongly supports a pathogenic classification, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-12.030	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.40	Destabilizing	0.1	5.82	Destabilizing	6.61	Destabilizing	2.22	Destabilizing	0.616	Likely Pathogenic	-4.80	Deleterious	1.000	Probably Damaging	0.980	Probably Damaging	3.68	Benign	0.01	Affected			0.3628	0.1874		-3	-3	-5.4	-16.04
c.1441C>A	H481N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H481N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools—Rosetta and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.229	Likely Pathogenic	0.381	Ambiguous	Likely Benign	0.16	Likely Benign	0.1	0.54	Ambiguous	0.35	Likely Benign	0.09	Likely Benign	0.205	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.68	Benign	0.57	Tolerated			0.1205	0.1631		2	1	-0.3	-23.04
c.250C>G	R84G 2D AIThe SynGAP1 missense variant R84G is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the majority of available predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar status of “Uncertain.” Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500					Uncertain		1				-6.627	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.139	Likely Benign	-2.64	Deleterious	0.962	Probably Damaging	0.726	Possibly Damaging	3.68	Benign	0.00	Affected	4.32	1	0.3387	0.3391		-3	-2	4.1	-99.14
c.251G>A	R84H 2D AIThe SynGAP1 missense variant R84H is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Overall, the majority of standard predictors (four pathogenic vs. three benign) lean toward a pathogenic interpretation, and the high‑accuracy consensus does not overturn this trend. 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.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-7.333	In-Between	0.935	Likely Pathogenic	Ambiguous										0.147	Likely Benign	-1.77	Neutral	0.995	Probably Damaging	0.840	Possibly Damaging	3.68	Benign	0.00	Affected			0.2739	0.2426		2	0	1.3	-19.05
c.263T>A	V88E 2D AIThe SynGAP1 missense variant V88E is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of predictions (five benign vs. three pathogenic) and the SGM Consensus support a benign classification, whereas AlphaMissense‑Optimized alone suggests pathogenicity. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-7.978	In-Between	0.993	Likely Pathogenic	Likely Pathogenic										0.095	Likely Benign	-1.95	Neutral	0.001	Benign	0.000	Benign	3.68	Benign	0.00	Affected			0.1444	0.1725		-2	-2	-7.7	29.98
c.263T>G	V88G 2D AIThe SynGAP1 missense variant V88G is not 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) and Foldetta results are unavailable. Overall, the majority of predictions (5 benign vs. 4 pathogenic) and the lack of a ClinVar pathogenic classification suggest that V88G is most likely benign, with no contradiction to existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-8.588	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.084	Likely Benign	-2.40	Neutral	0.024	Benign	0.208	Benign	3.68	Benign	0.00	Affected			0.2608	0.2609		-1	-3	-4.6	-42.08
c.318G>C	R106S 2D AIThe SynGAP1 missense variant R106S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, 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, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence. Thus, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-2.651	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-1.87	Neutral	0.131	Benign	0.026	Benign	3.68	Benign	0.00	Affected			0.3050	0.4129		0	-1	3.7	-69.11
c.318G>T	R106S 2D AIThe SynGAP1 missense variant R106S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, 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, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence. Thus, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-2.651	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-1.87	Neutral	0.131	Benign	0.026	Benign	3.68	Benign	0.00	Affected			0.3050	0.4129		0	-1	3.7	-69.11
c.349A>T	S117C 2D AIThe SynGAP1 missense variant S117C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is 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		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-5.980	Likely Benign	0.201	Likely Benign	Likely Benign										0.246	Likely Benign	-1.81	Neutral	0.992	Probably Damaging	0.667	Possibly Damaging	3.68	Benign	0.00	Affected			0.1222	0.5057		0	-1	3.3	16.06
c.404G>C	R135P 2D AIThe SynGAP1 missense variant R135P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors that classify the variant as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy tools give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-9.512	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.139	Likely Benign	-3.19	Deleterious	0.609	Possibly Damaging	0.308	Benign	3.68	Benign	0.01	Affected			0.2052	0.4535		0	-2	2.9	-59.07
c.433A>G	K145E 2D AIThe SynGAP1 missense variant K145E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of high‑confidence tools predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-12.571	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.245	Likely Benign	-2.51	Deleterious	0.247	Benign	0.125	Benign	3.68	Benign	0.00	Affected			0.3638	0.1179		0	1	0.4	0.94
c.544T>A	S182T 2D AIThe SynGAP1 missense variant S182T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of available predictions (five benign vs three pathogenic) suggest a benign impact. This consensus does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-11.247	Likely Pathogenic	0.857	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-2.29	Neutral	0.231	Benign	0.081	Benign	3.68	Benign	0.00	Affected			0.1624	0.5657		1	1	0.1	14.03
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.1205T>A	L402Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402Q 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 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic based on the collective computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-13.403	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.93	Destabilizing	0.0	2.55	Destabilizing	2.74	Destabilizing	2.09	Destabilizing	0.523	Likely Pathogenic	-4.52	Deleterious	0.999	Probably Damaging	0.957	Probably Damaging	3.69	Benign	0.00	Affected			0.1384	0.1173		-2	-2	-7.3	14.97
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.1288A>C	M430L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, FoldX, Rosetta, PolyPhen‑2 (HumDiv and HumVar), SIFT, and REVEL; no tool predicts pathogenicity. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all available evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-5.873	Likely Benign	0.104	Likely Benign	Likely Benign	0.33	Likely Benign	0.1	-0.10	Likely Benign	0.12	Likely Benign	0.72	Ambiguous	0.107	Likely Benign	-1.07	Neutral	0.028	Benign	0.004	Benign	3.69	Benign	0.66	Tolerated			0.1767	0.5067		4	2	1.9	-18.03
c.1288A>T	M430L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, FoldX, Rosetta, PolyPhen‑2 (HumDiv and HumVar), SIFT, and REVEL; no tool predicts pathogenicity. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all available evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-5.873	Likely Benign	0.104	Likely Benign	Likely Benign	0.33	Likely Benign	0.1	-0.10	Likely Benign	0.12	Likely Benign	0.72	Ambiguous	0.107	Likely Benign	-1.07	Neutral	0.028	Benign	0.004	Benign	3.69	Benign	0.66	Tolerated			0.1767	0.5067		4	2	1.9	-18.03
c.3358G>A	G1120S 2D AIThe SynGAP1 missense variant G1120S is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that G1120S is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875											-4.959	Likely Benign	0.073	Likely Benign	Likely Benign										0.286	Likely Benign	-0.27	Neutral	0.451	Benign	0.209	Benign	3.69	Benign	0.77	Tolerated			0.2515	0.5311		1	0	-0.4	30.03
c.403C>G	R135G 2D AIThe SynGAP1 missense variant R135G is not reported in ClinVar and is absent from gnomAD. Consensus from standard in silico predictors shows a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments give a pathogenic result from AlphaMissense‑Optimized, an inconclusive SGM Consensus (a 2‑vs‑2 vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no Foldetta data. Because the majority of tools predict benign and the high‑accuracy methods are either pathogenic or inconclusive, the overall evidence leans toward a benign effect. This conclusion does not conflict with the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-5.799	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.240	Likely Benign	-3.17	Deleterious	0.000	Benign	0.000	Benign	3.69	Benign	0.01	Affected			0.3559	0.3273		-3	-2	4.1	-99.14
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.1208A>T	K403I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403I 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 FoldX, Rosetta, Foldetta, premPS, and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (nine pathogenic vs. five benign) and the high‑accuracy tools lean toward a pathogenic effect. Thus, 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	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-15.239	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.1	-0.46	Likely Benign	-0.15	Likely Benign	0.36	Likely Benign	0.519	Likely Pathogenic	-7.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.70	Benign	0.00	Affected			0.1223	0.4141		-2	-3	8.4	-15.01
c.251G>T	R84L 2D AIThe SynGAP1 missense variant R84L 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. ESM1b remains 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 indicates that R84L 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.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-7.579	In-Between	0.987	Likely Pathogenic	Likely Pathogenic										0.120	Likely Benign	-2.75	Deleterious	0.962	Probably Damaging	0.726	Possibly Damaging	3.70	Benign	0.00	Affected			0.1595	0.4653		-3	-2	8.3	-43.03
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.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.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.349A>C	S117R 2D AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and 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, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this 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		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.276	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.350G>T	S117I 2D AIThe SynGAP1 missense variant S117I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-5.483	Likely Benign	0.559	Ambiguous	Likely Benign										0.137	Likely Benign	-2.33	Neutral	0.971	Probably Damaging	0.598	Possibly Damaging	3.70	Benign	0.00	Affected			0.1060	0.5048		-1	-2	5.3	26.08
c.351C>A	S117R 2D AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) and the consensus evidence lean toward a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.144	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.351C>G	S117R 2D AIThe SynGAP1 missense variant S117R is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33432216‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a pathogenic 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		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625								6-33432216-C-G	1	6.20e-7	-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.144	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.404G>T	R135L 2D AIThe SynGAP1 missense variant R135L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also indicates pathogenicity. 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, support a pathogenic 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.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-7.372	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-3.61	Deleterious	0.308	Benign	0.122	Benign	3.70	Benign	0.01	Affected			0.1962	0.4727		-3	-2	8.3	-43.03
c.446A>G	K149R 2D AIThe SynGAP1 missense variant K149R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that K149R is most likely benign, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-8.237	Likely Pathogenic	0.406	Ambiguous	Likely Benign										0.143	Likely Benign	-1.70	Neutral	0.247	Benign	0.125	Benign	3.70	Benign	0.00	Affected			0.5639	0.1169	Weaken	3	2	-0.6	28.01
c.544T>G	S182A 2D AIThe SynGAP1 missense variant S182A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of standard predictors lean toward a benign impact, and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-9.417	Likely Pathogenic	0.838	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-2.26	Neutral	0.001	Benign	0.005	Benign	3.70	Benign	0.00	Affected			0.5466	0.4660	Weaken	1	1	2.6	-16.00
c.560T>C	L187P 2D AIThe SynGAP1 missense variant L187P is listed in gnomAD (ID 6‑33435202‑T‑C) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL and FATHMM, whereas the remaining tools—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 classifies the variant as Likely Pathogenic. No Foldetta stability result is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently reports no classification. 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								6-33435202-T-C	1	6.20e-7	-13.192	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.320	Likely Benign	-5.17	Deleterious	0.917	Possibly Damaging	0.548	Possibly Damaging	3.70	Benign	0.01	Affected	3.47	9	0.3604	0.1484		-3	-3	-5.4	-16.04
c.626T>C	V209A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V209A is reported in gnomAD (ID 6‑33435268‑T‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and FATHMM. In contrast, a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, and the combined Foldetta score are uncertain and therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that V209A is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125								6-33435268-T-C	1	6.20e-7	-9.796	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.3	1.85	Ambiguous	1.71	Ambiguous	1.60	Destabilizing	0.236	Likely Benign	-2.79	Deleterious	0.958	Probably Damaging	0.581	Possibly Damaging	3.70	Benign	0.02	Affected	3.41	13	0.2237	0.1919		0	0	-2.4	-28.05
c.227C>A	S76Y 2D AIThe SynGAP1 missense variant S76Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for S76Y, 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	0.444487	Uncertain	0.279	0.826	0.500											-4.243	Likely Benign	0.209	Likely Benign	Likely Benign										0.119	Likely Benign	-2.35	Neutral	0.972	Probably Damaging	0.831	Possibly Damaging	3.71	Benign	0.00	Affected			0.0540	0.4753		-3	-2	-0.5	76.10
c.227C>G	S76C 2D AIThe SynGAP1 missense variant S76C is listed in ClinVar with an “Uncertain” status (ClinVar ID 1951273.0) and is present in the gnomAD database (gnomAD ID 6‑33425835‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available for this variant. Overall, the majority of computational evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500					Uncertain		1	6-33425835-C-G	2	1.24e-6	-5.408	Likely Benign	0.100	Likely Benign	Likely Benign										0.076	Likely Benign	-1.78	Neutral	0.992	Probably Damaging	0.869	Possibly Damaging	3.71	Benign	0.00	Affected	4.32	1	0.0807	0.4787		0	-1	3.3	16.06
c.227C>T	S76F 2D AIThe SynGAP1 missense variant S76F is reported in ClinVar as “Not submitted” and is present in gnomAD (variant ID 6-33425835-C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion 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		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500								6-33425835-C-T	4	2.48e-6	-4.557	Likely Benign	0.197	Likely Benign	Likely Benign										0.082	Likely Benign	-2.40	Neutral	0.972	Probably Damaging	0.831	Possibly Damaging	3.71	Benign	0.00	Affected	4.32	1	0.0501	0.4887		-2	-3	3.6	60.10
c.245T>A	L82Q 2D AIThe SynGAP1 missense variant L82Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction. Foldetta results are unavailable. Overall, the majority of conventional tools lean toward benign, and the SGM Consensus supports this, but the AlphaMissense‑Optimized prediction introduces a pathogenic signal. Consequently, the variant is most likely benign based on the prevailing evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-7.576	In-Between	0.987	Likely Pathogenic	Likely Pathogenic										0.079	Likely Benign	-2.16	Neutral	0.939	Possibly Damaging	0.114	Benign	3.71	Benign	0.00	Affected			0.1150	0.0790		-2	-2	-7.3	14.97
c.250C>A	R84S 2D AIThe SynGAP1 missense variant R84S is not reported in ClinVar and has no gnomAD entry. Prediction tools show mixed results: benign predictions come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta stability analysis is unavailable. Overall, the majority of tools lean toward a benign interpretation, but a substantial subset predicts pathogenicity, leaving the variant’s effect uncertain. Based on the current predictions, R84S is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-6.233	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.103	Likely Benign	-2.18	Neutral	0.962	Probably Damaging	0.726	Possibly Damaging	3.71	Benign	0.00	Affected			0.2966	0.4139		0	-1	3.7	-69.11
c.350G>A	S117N 2D AIThe SynGAP1 missense variant S117N 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, 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 from multiple prediction algorithms and consensus analyses indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-5.704	Likely Benign	0.489	Ambiguous	Likely Benign										0.067	Likely Benign	-1.06	Neutral	0.005	Benign	0.003	Benign	3.71	Benign	0.01	Affected			0.1491	0.4530		1	1	-2.7	27.03
c.3976C>A	P1326T 2D AIThe SynGAP1 missense variant P1326T is reported in gnomAD (ID 6‑33451850‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the same four high‑accuracy tools) is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P1326T is most likely benign, and this assessment does not contradict any ClinVar classification because no ClinVar variant is listed. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875								6-33451850-C-A			-5.755	Likely Benign	0.117	Likely Benign	Likely Benign										0.135	Likely Benign	-0.26	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.71	Benign	0.00	Affected	3.77	5	0.1955	0.5517		-1	0	0.9	3.99
c.434A>G	K145R 2D AIThe SynGAP1 missense variant K145R is listed in gnomAD (ID 6‑33432731‑A‑G) 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 change as benign or likely benign. Only SIFT predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is currently assigned to the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625								6-33432731-A-G	1	6.20e-7	-7.685	In-Between	0.214	Likely Benign	Likely Benign										0.128	Likely Benign	-1.58	Neutral	0.399	Benign	0.212	Benign	3.71	Benign	0.00	Affected	3.61	5	0.4661	0.1242		2	3	-0.6	28.01
c.436T>G	S146A 2D AIThe SynGAP1 missense variant S146A is not reported 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-14.042	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign										0.097	Likely Benign	-1.81	Neutral	0.000	Benign	0.002	Benign	3.71	Benign	0.00	Affected			0.4435	0.3708		1	1	2.6	-16.00
c.586T>G	L196V 2D AIThe SynGAP1 missense variant L196V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of evidence (five benign vs three pathogenic) points to a benign impact. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-8.702	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous										0.106	Likely Benign	-2.31	Neutral	0.243	Benign	0.097	Benign	3.71	Benign	0.01	Affected			0.1436	0.2850		2	1	0.4	-14.03
c.244C>G	L82V 2D AIThe SynGAP1 missense variant L82V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33425852‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore indicate a benign likelihood: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375								6-33425852-C-G			-6.701	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.065	Likely Benign	-1.13	Neutral	0.371	Benign	0.024	Benign	3.72	Benign	0.00	Affected	4.32	1	0.1467	0.2353		1	2	0.4	-14.03
c.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.3208A>T	R1070W 2D AIThe SynGAP1 missense variant R1070W is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the majority of tools and the SGM‑Consensus support a pathogenic effect, so the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-8.063	Likely Pathogenic	0.743	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.956	Probably Damaging	3.72	Benign	0.00	Affected			0.1195	0.4293		2	-3	3.6	30.03
c.559C>A	L187M 2D AIThe SynGAP1 missense variant L187M is not 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. Those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, which would assess protein‑folding stability, has no available output for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, 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.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-8.814	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.136	Likely Benign	-1.35	Neutral	0.971	Probably Damaging	0.641	Possibly Damaging	3.72	Benign	0.02	Affected			0.0848	0.3613		4	2	-1.9	18.03
c.560T>A	L187Q 2D AIThe SynGAP1 missense variant L187Q is not 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 likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for the SynGAP1 L187Q variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-13.063	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.322	Likely Benign	-4.31	Deleterious	0.917	Possibly Damaging	0.548	Possibly Damaging	3.72	Benign	0.00	Affected			0.1251	0.1060		-2	-2	-7.3	14.97
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.1204C>A	L402M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402M is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-6.991	Likely Benign	0.305	Likely Benign	Likely Benign	0.12	Likely Benign	0.0	1.33	Ambiguous	0.73	Ambiguous	0.80	Ambiguous	0.071	Likely Benign	-0.99	Neutral	0.994	Probably Damaging	0.938	Probably Damaging	3.73	Benign	0.02	Affected			0.1064	0.4095		4	2	-1.9	18.03
c.1208A>C	K403T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403T missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. In contrast, 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 all classify the variant as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; SGM‑Consensus predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Other stability predictors (FoldX, Rosetta, premPS) are also uncertain. Overall, the consensus of the majority of tools indicates a pathogenic effect. This conclusion is not contradicted by 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	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-13.135	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.41	Ambiguous	0.1	0.59	Ambiguous	1.00	Ambiguous	0.67	Ambiguous	0.522	Likely Pathogenic	-5.43	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.73	Benign	0.01	Affected			0.1861	0.4230		0	-1	3.2	-27.07
c.1209A>C	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1209A>T	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1462A>T	T488S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T488S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, and Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of standard tools lean toward a benign interpretation, but the high‑accuracy consensus is split, leaving the variant’s impact ambiguous. No ClinVar annotation contradicts these predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-7.662	In-Between	0.745	Likely Pathogenic	Likely Benign	0.35	Likely Benign	0.1	0.90	Ambiguous	0.63	Ambiguous	0.77	Ambiguous	0.257	Likely Benign	-3.51	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.73	Benign	0.31	Tolerated			0.2256	0.2813		1	1	-0.1	-14.03
c.149T>A	I50N 2D AIThe SynGAP1 missense variant I50N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign. Foldetta results are unavailable. Overall, the predictions are mixed, with an equal split between benign and pathogenic calls, but the most reliable single‑tool prediction (AlphaMissense‑Optimized) and the majority of individual tools lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-7.091	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.135	Likely Benign	-2.37	Neutral	0.842	Possibly Damaging	0.272	Benign	3.73	Benign	0.00	Affected			0.0824	0.0412		-2	-3	-8.0	0.94
c.1945A>C	M649L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN and AlphaMissense‑Default, while premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta predicts benign stability. Overall, the preponderance of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-5.210	Likely Benign	0.745	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.4	0.26	Likely Benign	0.23	Likely Benign	0.64	Ambiguous	0.294	Likely Benign	-2.99	Deleterious	0.009	Benign	0.007	Benign	3.73	Benign	0.15	Tolerated			0.1361	0.4025		4	2	1.9	-18.03
c.1945A>T	M649L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and AlphaMissense‑Default, while premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-5.210	Likely Benign	0.745	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.4	0.26	Likely Benign	0.23	Likely Benign	0.64	Ambiguous	0.294	Likely Benign	-2.99	Deleterious	0.009	Benign	0.007	Benign	3.73	Benign	0.15	Tolerated			0.1361	0.4025		4	2	1.9	-18.03
c.257T>A	V86D 2D AIThe SynGAP1 missense variant V86D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on benign impact include REVEL, PROVEAN, and FATHMM, whereas those that agree on pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans benign (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, whereas the high‑accuracy consensus suggests benign. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for V86D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-7.141	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.147	Likely Benign	-2.38	Neutral	0.824	Possibly Damaging	0.485	Possibly Damaging	3.73	Benign	0.00	Affected			0.1590	0.1047		-2	-3	-7.7	15.96
c.266C>T	P89L 2D AISynGAP1 missense variant P89L 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, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM Consensus (derived 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 tools favor a pathogenic effect, but the evidence is not unanimous. Therefore, the variant is most likely pathogenic according to the current predictions, and this assessment does not contradict its ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500					Uncertain		2				-6.775	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.119	Likely Benign	-3.29	Deleterious	0.889	Possibly Damaging	0.058	Benign	3.73	Benign	0.00	Affected	4.32	1	0.2399	0.5638		-3	-3	5.4	16.04
c.2830G>C	G944R 2D AIThe SynGAP1 missense variant G944R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G944R, 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		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750											-6.577	Likely Benign	0.359	Ambiguous	Likely Benign										0.459	Likely Benign	-1.82	Neutral	0.639	Possibly Damaging	0.299	Benign	3.73	Benign	0.00	Affected			0.1030	0.4733		-3	-2	-4.1	99.14
c.349A>G	S117G 2D AIThe SynGAP1 missense variant S117G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-3.280	Likely Benign	0.174	Likely Benign	Likely Benign										0.122	Likely Benign	-1.59	Neutral	0.390	Benign	0.066	Benign	3.73	Benign	0.01	Affected			0.2113	0.4627		1	0	0.4	-30.03
c.3976C>G	P1326A 2D AIThe SynGAP1 missense variant P1326A 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		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875											-4.450	Likely Benign	0.068	Likely Benign	Likely Benign										0.097	Likely Benign	-0.76	Neutral	0.996	Probably Damaging	0.986	Probably Damaging	3.73	Benign	0.00	Affected			0.3728	0.4333		1	-1	3.4	-26.04
c.409C>A	L137I 2D AIThe SynGAP1 missense variant L137I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 3 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.870	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.22	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.0932	0.3102		2	2	0.7	0.00
c.409C>G	L137V 2D AIThe SynGAP1 missense variant L137V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.621	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.118	Likely Benign	-1.75	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.1533	0.2612		2	1	0.4	-14.03
c.431C>T	T144M 2D AIThe SynGAP1 missense variant T144M is listed in ClinVar with an “Uncertain” status (ClinVar ID 2231966.0) and is present in the gnomAD database (gnomAD ID 6‑33432728‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of computational predictions lean toward a pathogenic impact, and this assessment does not contradict the ClinVar designation of uncertainty. 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					Uncertain		2	6-33432728-C-T	2	1.30e-6	-11.228	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous										0.118	Likely Benign	-3.16	Deleterious	0.913	Possibly Damaging	0.333	Benign	3.73	Benign	0.00	Affected	3.61	5	0.1504	0.6510		-1	-1	2.6	30.09
c.571A>T	S191C 2D AIThe SynGAP1 missense variant S191C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—leans pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of tools and the SGM Consensus predict a pathogenic impact, so 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.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.009	In-Between	0.709	Likely Pathogenic	Likely Benign										0.288	Likely Benign	-3.39	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.73	Benign	0.00	Affected			0.1064	0.7134		0	-1	3.3	16.06
c.1417G>A	V473I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473I is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438449‑G‑A). Functional prediction tools that agree on benign impact include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions are provided by both polyPhen‑2 HumDiv and HumVar. Predictions that are inconclusive are AlphaMissense‑Default, ESM1b, Foldetta, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to no majority, and Foldetta is uncertain. Overall, the balance of evidence favors a benign effect for V473I, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000					Uncertain		1	6-33438449-G-A	1	6.20e-7	-7.481	In-Between	0.418	Ambiguous	Likely Benign	-0.12	Likely Benign	0.0	1.20	Ambiguous	0.54	Ambiguous	-0.06	Likely Benign	0.203	Likely Benign	-0.91	Neutral	0.929	Possibly Damaging	0.917	Probably Damaging	3.74	Benign	0.18	Tolerated	3.37	34	0.0568	0.3335		3	4	0.3	14.03
c.149T>G	I50S 2D AIThe SynGAP1 I50S missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic impact. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore point to a benign outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-4.257	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-2.03	Neutral	0.334	Benign	0.099	Benign	3.74	Benign	0.00	Affected			0.2626	0.0800		-1	-2	-5.3	-26.08
c.257T>G	V86G 2D AIThe SynGAP1 missense variant V86G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which evaluates protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence (five pathogenic versus four benign predictions) indicates that V86G is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-4.212	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.130	Likely Benign	-2.50	Deleterious	0.307	Benign	0.824	Possibly Damaging	3.74	Benign	0.00	Affected			0.2321	0.2547		-1	-3	-4.6	-42.08
c.260C>G	S87C 2D AIThe SynGAP1 missense variant S87C is not 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 methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is uncertain due to a 2‑to‑2 split; and Foldetta, which assesses protein‑folding stability, is unavailable for this variant. Overall, the majority of available predictions (five pathogenic versus three benign) indicate a likely pathogenic impact. 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.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-8.769	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-2.14	Neutral	0.880	Possibly Damaging	0.700	Possibly Damaging	3.74	Benign	0.00	Affected			0.0794	0.4849		0	-1	3.3	16.06
c.260C>T	S87F 2D AIThe SynGAP1 missense variant S87F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Therefore, 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.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-9.673	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.054	Likely Benign	-2.34	Neutral	0.676	Possibly Damaging	0.485	Possibly Damaging	3.74	Benign	0.00	Affected			0.0493	0.4937		-3	-2	3.6	60.10
c.262G>C	V88L 2D AIThe SynGAP1 V88L variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of tools suggest a benign impact, but the high‑accuracy predictions are conflicting. The variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-5.808	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.066	Likely Benign	-0.79	Neutral	0.225	Benign	0.027	Benign	3.74	Benign	0.00	Affected			0.1457	0.4562		2	1	-0.4	14.03
c.262G>T	V88L 2D AIThe SynGAP1 missense variant V88L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM, whereas SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect; a Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-5.808	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.066	Likely Benign	-0.79	Neutral	0.225	Benign	0.027	Benign	3.74	Benign	0.00	Affected			0.1457	0.4562		2	1	-0.4	14.03
c.265C>A	P89T 2D AIThe SynGAP1 missense variant P89T has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence leans toward a benign effect, but the presence of a pathogenic prediction from AlphaMissense‑Optimized introduces uncertainty. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-5.429	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-2.49	Neutral	0.588	Possibly Damaging	0.036	Benign	3.74	Benign	0.00	Affected			0.1786	0.4702		0	-1	0.9	3.99
c.266C>A	P89Q 2D AIThe SynGAP1 missense variant P89Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates 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.			0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-4.779	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.107	Likely Benign	-2.63	Deleterious	0.642	Possibly Damaging	0.038	Benign	3.74	Benign	0.00	Affected			0.1633	0.4310		0	-1	-1.9	31.01
c.2941G>C	G981R 2D AIThe SynGAP1 missense variant G981R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely benign based on current predictive tools. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625											-1.264	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.207	Likely Benign	-2.11	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	3.74	Benign	0.00	Affected			0.0990	0.4776		-3	-2	-4.1	99.14
c.3209G>T	R1070M 2D AIThe SynGAP1 missense variant R1070M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus benign call and the absence of pathogenic predictions from the most reliable tools, suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-6.455	Likely Benign	0.917	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-2.27	Neutral	0.995	Probably Damaging	0.907	Possibly Damaging	3.74	Benign	0.00	Affected			0.1661	0.4324		0	-1	6.4	-24.99
c.3976C>T	P1326S 2D AIThe SynGAP1 missense variant P1326S is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33451850‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence—including the high‑accuracy tools—supports a benign classification. This conclusion does not contradict the ClinVar status, which currently has no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875								6-33451850-C-T			-5.221	Likely Benign	0.121	Likely Benign	Likely Benign										0.107	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.74	Benign	0.00	Affected	3.77	5	0.3722	0.4563		-1	1	0.8	-10.04
c.421A>G	I141V 2D AIThe SynGAP1 I141V missense variant is catalogued in gnomAD (ID 6‑33432718‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM) and pathogenic (SIFT, AlphaMissense‑Default). The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the preponderance of evidence points to a benign effect, and this assessment aligns with the lack of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500								6-33432718-A-G	1	6.42e-7	-4.030	Likely Benign	0.785	Likely Pathogenic	Ambiguous										0.125	Likely Benign	-0.58	Neutral	0.016	Benign	0.021	Benign	3.74	Benign	0.03	Affected	3.61	5	0.1101	0.3464		3	4	-0.3	-14.03
c.448C>A	L150I 2D AIThe SynGAP1 missense variant L150I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a likely pathogenic impact for the variant. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.118	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous										0.080	Likely Benign	-1.25	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.0894	0.3468		2	2	0.7	0.00
c.448C>G	L150V 2D AIThe SynGAP1 missense variant L150V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.375	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.84	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.1473	0.3178		2	1	0.4	-14.03
c.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.1993T>G	Y665D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665D is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as Uncertain. No evidence from these tools contradicts the ClinVar status, which is currently unreported. Overall, the balance of evidence—seven pathogenic versus four benign predictions, with a pathogenic consensus from SGM‑Consensus—suggests the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-10.101	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign	1.15	Ambiguous	0.2	1.30	Ambiguous	1.23	Ambiguous	0.15	Likely Benign	0.227	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	1.00	Tolerated			0.3838	0.0573		-4	-3	-2.2	-48.09
c.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.259T>C	S87P 2D AIThe SynGAP1 missense variant S87P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-8.566	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.073	Likely Benign	-2.04	Neutral	0.676	Possibly Damaging	0.307	Benign	3.75	Benign	0.00	Affected			0.1639	0.4260		1	-1	-0.8	10.04
c.260C>A	S87Y 2D AIThe SynGAP1 missense variant S87Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Therefore, 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.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-10.410	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.052	Likely Benign	-2.20	Neutral	0.880	Possibly Damaging	0.608	Possibly Damaging	3.75	Benign	0.00	Affected			0.0522	0.4798		-3	-2	-0.5	76.10
c.263T>C	V88A 2D AIThe SynGAP1 missense variant V88A is listed in ClinVar (ID 2656486.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default, AlphaMissense‑Optimized, and SIFT. 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 pathogenic, while the SGM‑Consensus (majority vote) is benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500					Uncertain		1				-5.860	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.050	Likely Benign	-1.22	Neutral	0.053	Benign	0.008	Benign	3.75	Benign	0.00	Affected	4.32	1	0.3563	0.2769		0	0	-2.4	-28.05
c.2942G>A	G981D 2D AIThe SynGAP1 missense variant G981D 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 outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Taken together, the balance of evidence leans toward a benign interpretation; there is no ClinVar entry to contradict this assessment. 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		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625											-5.280	Likely Benign	0.945	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-1.64	Neutral	1.000	Probably Damaging	0.985	Probably Damaging	3.75	Benign	0.00	Affected			0.1961	0.2868		1	-1	-3.1	58.04
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.3208A>G	R1070G 2D AIThe SynGAP1 missense variant R1070G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from standard in silico predictors shows five tools (REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized) classifying it as benign, while four (PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default) predict pathogenicity. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign effect. This conclusion does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-4.731	Likely Benign	0.568	Likely Pathogenic	Likely Benign										0.149	Likely Benign	-2.88	Deleterious	0.789	Possibly Damaging	0.258	Benign	3.75	Benign	0.01	Affected			0.3150	0.4070		-3	-2	4.1	-99.14
c.4013G>C	R1338P 2D AISynGAP1 missense variant R1338P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the available predictions are evenly split between benign and pathogenic, with no high‑accuracy tool providing definitive support. Therefore, the variant is most likely pathogenic based on the balance of evidence, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000											-3.678	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.191	Likely Benign	-3.43	Deleterious	0.931	Possibly Damaging	0.410	Benign	3.75	Benign	0.01	Affected			0.2065	0.5095		0	-2	2.9	-59.07
c.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.623C>G	P208R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The majority of other in silico predictors (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact, while Rosetta remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, with no contradiction to ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-11.929	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	5.25	Destabilizing	1.6	1.39	Ambiguous	3.32	Destabilizing	1.16	Destabilizing	0.472	Likely Benign	-7.50	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.00	Affected			0.1676	0.3118		0	-2	-2.9	59.07
c.623C>T	P208L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P208L has no ClinVar entry and is present in gnomAD (ID 6‑33435265‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, while those that agree on a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are inconclusive are Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125								6-33435265-C-T	1	6.20e-7	-10.013	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	2.35	Destabilizing	0.5	0.04	Likely Benign	1.20	Ambiguous	0.67	Ambiguous	0.466	Likely Benign	-8.49	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.01	Affected	3.44	12	0.2219	0.6191		-3	-3	5.4	16.04
c.1207A>C	K403Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The premPS assessment is uncertain and does not influence the overall consensus. High‑accuracy analyses show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-12.479	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.36	Likely Benign	0.0	0.27	Likely Benign	0.32	Likely Benign	0.70	Ambiguous	0.376	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.76	Benign	0.01	Affected			0.4405	0.1954		1	1	0.4	-0.04
c.149T>C	I50T 2D AIThe SynGAP1 missense variant I50T is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic effect. 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. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments therefore point to a benign outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is benign, and Foldetta data are missing. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-5.121	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-1.61	Neutral	0.092	Benign	0.037	Benign	3.76	Benign	0.00	Affected			0.0950	0.0708		0	-1	-5.2	-12.05
c.150C>G	I50M 2D AIThe SynGAP1 missense variant I50M 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. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, 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 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 preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that the I50M variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-5.707	Likely Benign	0.383	Ambiguous	Likely Benign										0.030	Likely Benign	-0.95	Neutral	0.637	Possibly Damaging	0.202	Benign	3.76	Benign	0.00	Affected			0.0603	0.2524		2	1	-2.6	18.03
c.265C>T	P89S 2D AIThe SynGAP1 missense variant P89S is not reported 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 FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote) indicates likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, and this assessment does not contradict the absence of a ClinVar classification. 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		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-5.198	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-2.40	Neutral	0.225	Benign	0.020	Benign	3.76	Benign	0.00	Affected			0.3459	0.4191		1	-1	0.8	-10.04
c.4012C>G	R1338G 2D AIThe SynGAP1 R1338G variant has no ClinVar record (status: None) and is not present in gnomAD. Prediction tools that agree on benign impact include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the predictions are evenly split between benign and pathogenic, leaving the variant’s clinical significance uncertain. This uncertainty 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.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000											-3.696	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.134	Likely Benign	-3.73	Deleterious	0.795	Possibly Damaging	0.232	Benign	3.76	Benign	0.01	Affected			0.3468	0.3874		-3	-2	4.1	-99.14
c.404G>A	R135Q 2D AIThe SynGAP1 missense variant R135Q is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33432701‑G‑A). Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions come from SIFT, ESM1b, and AlphaMissense‑Default. The remaining high‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑to‑2 tie, and Foldetta stability analysis is not available. Overall, the balance of evidence favors a benign effect, and this conclusion does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250					Uncertain		1	6-33432701-G-A	5	3.84e-6	-8.011	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous										0.087	Likely Benign	-1.94	Neutral	0.327	Benign	0.100	Benign	3.76	Benign	0.02	Affected	3.61	5	0.3153	0.2741		1	1	1.0	-28.06
c.430A>C	T144P 2D AIThe SynGAP1 missense variant T144P 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of predictions and the consensus call indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-11.920	Likely Pathogenic	0.775	Likely Pathogenic	Likely Benign										0.159	Likely Benign	-2.66	Deleterious	0.000	Benign	0.000	Benign	3.76	Benign	0.00	Affected			0.2508	0.5271		0	-1	-0.9	-3.99
c.431C>A	T144K 2D AIThe SynGAP1 T144K variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, 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 further support a deleterious outcome: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-15.436	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-2.83	Deleterious	0.180	Benign	0.063	Benign	3.76	Benign	0.00	Affected			0.1462	0.3179		0	-1	-3.2	27.07
c.572G>T	S191I 2D AIThe SynGAP1 missense variant S191I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. When the predictions are grouped by consensus, four tools favor benign and four favor pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Taken together, the majority of evidence, including the SGM Consensus, points to 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		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-11.271	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.283	Likely Benign	-4.51	Deleterious	0.421	Benign	0.086	Benign	3.76	Benign	0.00	Affected			0.0954	0.6842		-1	-2	5.3	26.08
c.622C>A	P208T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta; premPS and Rosetta are uncertain. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta also predicts pathogenic. With the majority of tools, including the high‑accuracy ones, indicating pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-9.016	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	3.20	Destabilizing	0.5	1.27	Ambiguous	2.24	Destabilizing	0.94	Ambiguous	0.270	Likely Benign	-6.80	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.76	Benign	0.01	Affected			0.1857	0.5197		0	-1	0.9	3.99
c.1216T>G	Y406D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406D is not 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. In contrast, the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic,” while premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-14.832	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.82	Destabilizing	0.3	4.28	Destabilizing	4.05	Destabilizing	0.98	Ambiguous	0.347	Likely Benign	-7.64	Deleterious	0.999	Probably Damaging	0.950	Probably Damaging	3.77	Benign	0.01	Affected			0.4439	0.0903		-4	-3	-2.2	-48.09
c.167T>C	L56P 2D AIThe SynGAP1 missense variant L56P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. 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 score (Likely Pathogenic). 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) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-9.991	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-2.62	Deleterious	0.943	Possibly Damaging	0.944	Probably Damaging	3.77	Benign	0.00	Affected			0.3806	0.1342		-3	-3	-5.4	-16.04
c.226T>C	S76P 2D AIThe SynGAP1 missense variant S76P is not reported 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 points to a benign effect for S76P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500											-3.833	Likely Benign	0.076	Likely Benign	Likely Benign										0.058	Likely Benign	-1.64	Neutral	0.909	Possibly Damaging	0.665	Possibly Damaging	3.77	Benign	0.00	Affected			0.1790	0.4138		1	-1	-0.8	10.04
c.265C>G	P89A 2D AIThe SynGAP1 missense variant P89A is listed in ClinVar (ID 1031674.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a “Likely Benign” outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictions indicate a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Thus, the variant is most likely benign based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500					Uncertain		2				-5.778	Likely Benign	0.920	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-2.47	Neutral	0.225	Benign	0.020	Benign	3.77	Benign	0.00	Affected	4.32	1	0.3407	0.3768		1	-1	3.4	-26.04
c.2830G>A	G944S 2D AIThe SynGAP1 missense variant G944S is listed in ClinVar as a benign alteration (ClinVar ID 833552.0) and is present in the gnomAD database (gnomAD ID 6‑33443382‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available for this variant. Overall, the majority of computational evidence supports a benign classification, which aligns with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750					Benign		1	6-33443382-G-A	13	8.05e-6	-5.303	Likely Benign	0.082	Likely Benign	Likely Benign										0.223	Likely Benign	-0.75	Neutral	0.007	Benign	0.004	Benign	3.77	Benign	0.00	Affected	4.32	4	0.2471	0.5502		1	0	-0.4	30.03
c.469C>T	R157C 2D AIThe SynGAP1 missense variant R157C is listed in gnomAD (ID 6‑33432766‑C‑T) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (which is “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 assessments therefore indicate a likely pathogenic consensus from SGM‑Consensus, an uncertain AlphaMissense‑Optimized score, and no Foldetta data. Overall, the majority of evidence points to a pathogenic effect, 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 Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375								6-33432766-C-T	7	4.34e-6	-11.524	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-4.02	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.77	Benign	0.00	Affected	3.74	4	0.3696	0.2092		-3	-4	7.0	-53.05
c.490C>G	R164G 2D AIThe SynGAP1 missense variant R164G has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split opinion: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus remains Likely Pathogenic, AlphaMissense‑Optimized is inconclusive, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact. Because there is no ClinVar classification to oppose this, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250											-12.416	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-3.01	Deleterious	0.487	Possibly Damaging	0.272	Benign	3.77	Benign	0.00	Affected			0.3657	0.3631		-3	-2	4.1	-99.14
c.491G>C	R164P 2D AIThe SynGAP1 missense variant R164P is reported in gnomAD (ID 6‑33432788‑G‑C) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an Uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the majority of high‑confidence tools predict pathogenicity, and this assessment does not contradict any ClinVar status (none is available). Therefore, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250								6-33432788-G-C	1	6.20e-7	-12.792	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous										0.339	Likely Benign	-3.42	Deleterious	0.910	Possibly Damaging	0.578	Possibly Damaging	3.77	Benign	0.00	Affected	3.74	4	0.2408	0.4730		-2	0	2.9	-59.07
c.547C>T	H183Y 2D AIThe SynGAP1 H183Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-9.481	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.250	Likely Benign	-4.48	Deleterious	0.818	Possibly Damaging	0.255	Benign	3.77	Benign	0.00	Affected			0.0831	0.4406		0	2	1.9	26.03
c.571A>G	S191G 2D AIThe SynGAP1 missense variant S191G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also leans toward benign (two benign versus two uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S191G is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.161	In-Between	0.506	Ambiguous	Likely Benign										0.173	Likely Benign	-2.43	Neutral	0.131	Benign	0.058	Benign	3.77	Benign	0.03	Affected			0.2893	0.5335		1	0	0.4	-30.03
c.71T>A	V24E 2D AIThe SynGAP1 missense variant V24E 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, the SGM‑Consensus also indicates Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-3.397	Likely Benign	0.517	Ambiguous	Likely Benign										0.171	Likely Benign	-1.73	Neutral	0.198	Benign	0.074	Benign	3.77	Benign	0.00	Affected			0.1133	0.2415		-2	-2	-7.7	29.98
c.71T>G	V24G 2D AIThe SynGAP1 missense variant V24G is not reported in ClinVar (ClinVar status: not present) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-2.673	Likely Benign	0.256	Likely Benign	Likely Benign										0.178	Likely Benign	-1.67	Neutral	0.026	Benign	0.049	Benign	3.77	Benign	0.00	Affected			0.2081	0.3105		-1	-3	-4.6	-42.08
c.1216T>A	Y406N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406N 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 and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change 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) reports a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. Taken together, the preponderance of evidence points to a pathogenic effect for Y406N, 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	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-13.206	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.1	2.88	Destabilizing	2.89	Destabilizing	1.58	Destabilizing	0.288	Likely Benign	-7.11	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	3.78	Benign	0.02	Affected			0.2532	0.1071		-2	-2	-2.2	-49.07
c.1217A>G	Y406C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406C 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 predict a pathogenic impact: FoldX, Rosetta, 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, also indicates a likely pathogenic outcome, and the Foldetta stability assessment (combining FoldX‑MD and Rosetta) predicts a destabilizing, pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while both SGM‑Consensus and Foldetta are pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for Y406C, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-9.954	Likely Pathogenic	0.810	Likely Pathogenic	Ambiguous	2.47	Destabilizing	0.2	3.22	Destabilizing	2.85	Destabilizing	1.27	Destabilizing	0.229	Likely Benign	-6.72	Deleterious	0.998	Probably Damaging	0.851	Possibly Damaging	3.78	Benign	0.01	Affected			0.3026	0.2861		0	-2	3.8	-60.04
c.226T>A	S76T 2D AIThe SynGAP1 missense variant S76T 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 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		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500											-4.000	Likely Benign	0.068	Likely Benign	Likely Benign										0.038	Likely Benign	-0.73	Neutral	0.805	Possibly Damaging	0.483	Possibly Damaging	3.78	Benign	0.00	Affected			0.1117	0.4774		1	1	0.1	14.03
c.3209G>C	R1070T 2D AIThe SynGAP1 missense variant R1070T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-5.093	Likely Benign	0.860	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-2.35	Neutral	0.948	Possibly Damaging	0.507	Possibly Damaging	3.78	Benign	0.01	Affected	3.77	5	0.1634	0.4727		-1	-1	3.8	-55.08
c.3209_3210delinsCA	R1070T 2D AIThe SynGAP1 missense variant R1070T is listed in ClinVar (ID 2759838.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (which aggregates these three benign calls with the pathogenic AlphaMissense‑Default to yield a Likely Benign verdict). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and no Foldetta stability data is available. Overall, the balance of evidence leans toward a benign impact, which is consistent with the ClinVar “Uncertain” status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875					Uncertain		1				-5.093	Likely Benign	0.860	Likely Pathogenic	Ambiguous												-2.35	Neutral	0.948	Possibly Damaging	0.507	Possibly Damaging	3.78	Benign	0.01	Affected	3.77	5	0.1634	0.4727		-1	-1	3.8	-55.08
c.4013G>T	R1338L 2D AIThe SynGAP1 missense variant R1338L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451887‑G‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, 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 results are unavailable. 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. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000								6-33451887-G-T			-3.359	Likely Benign	0.587	Likely Pathogenic	Likely Benign										0.232	Likely Benign	-3.65	Deleterious	0.001	Benign	0.001	Benign	3.78	Benign	0.01	Affected	3.77	5	0.2066	0.5307		-2	-3	8.3	-43.03
c.463A>T	S155C 2D AIThe SynGAP1 missense variant S155C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that 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 lean toward pathogenicity, but this conclusion conflicts with the benign prediction from AlphaMissense‑Optimized and the lack of ClinVar evidence. Thus, the variant is most likely pathogenic based on the prevailing predictions, though the evidence is not unequivocal. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.903	Likely Pathogenic	0.756	Likely Pathogenic	Likely Benign										0.238	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.78	Benign	0.00	Affected			0.0826	0.5681		0	-1	3.3	16.06
c.571A>C	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.324	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.572G>A	S191N 2D AIThe SynGAP1 missense variant S191N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools report an uncertain outcome: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign (2 benign vs. 1 pathogenic). AlphaMissense‑Optimized remains uncertain, and Foldetta folding‑stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact for S191N, and this conclusion does not contradict any ClinVar annotation, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.887	In-Between	0.830	Likely Pathogenic	Ambiguous										0.148	Likely Benign	-2.21	Neutral	0.596	Possibly Damaging	0.260	Benign	3.78	Benign	0.03	Affected			0.1366	0.5898		1	1	-2.7	27.03
c.573T>A	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.573T>G	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.616A>C	I206L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I206L is not 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), SIFT, FATHMM, and Foldetta. Those that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. Uncertain or inconclusive results come from premPS, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta predicts a benign outcome. Overall, the majority of tools (seven benign vs two pathogenic) support a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-9.488	Likely Pathogenic	0.790	Likely Pathogenic	Ambiguous	0.05	Likely Benign	0.1	0.75	Ambiguous	0.40	Likely Benign	0.78	Ambiguous	0.080	Likely Benign	-1.72	Neutral	0.004	Benign	0.012	Benign	3.78	Benign	0.08	Tolerated			0.0632	0.3608		2	2	-0.7	0.00
c.623C>A	P208Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Two tools give uncertain results (AlphaMissense‑Optimized and Rosetta) and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Pathogenic, reinforcing a deleterious prediction. Overall, the evidence strongly favors a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-9.746	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	3.30	Destabilizing	0.7	0.75	Ambiguous	2.03	Destabilizing	1.23	Destabilizing	0.411	Likely Benign	-6.78	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.78	Benign	0.00	Affected			0.1570	0.4663		0	-1	-1.9	31.01
c.1207A>G	K403E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for K403E, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-15.279	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.01	Ambiguous	0.1	0.79	Ambiguous	0.90	Ambiguous	0.70	Ambiguous	0.445	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.981	Probably Damaging	3.79	Benign	0.04	Affected			0.3650	0.1715		0	1	0.4	0.94
c.167T>A	L56Q 2D AIThe SynGAP1 missense variant L56Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (5 pathogenic vs 3 benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-11.064	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous										0.293	Likely Benign	-2.03	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.79	Benign	0.00	Affected			0.1083	0.0842		-2	-2	-7.3	14.97
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.350G>C	S117T 2D AIThe SynGAP1 missense variant S117T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-4.602	Likely Benign	0.142	Likely Benign	Likely Benign										0.089	Likely Benign	-0.98	Neutral	0.608	Possibly Damaging	0.092	Benign	3.79	Benign	0.02	Affected			0.1527	0.5505		1	1	0.1	14.03
c.356A>T	E119V 2D AISynGAP1 missense variant E119V 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, ESM1b, FATHMM, and polyPhen‑2 HumVar, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy methods are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie and is therefore unavailable, and Foldetta results are not provided. Consequently, the evidence does not strongly support either outcome. The variant is most likely inconclusive; it does not clearly favor benign or pathogenic status, and this lack of consensus does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-5.696	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.151	Likely Benign	-2.78	Deleterious	0.596	Possibly Damaging	0.189	Benign	3.79	Benign	0.00	Affected			0.1152	0.7753		-2	-2	7.7	-29.98
c.400A>T	S134C 2D AIThe SynGAP1 missense variant S134C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen2_HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, 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 pathogenic; Foldetta results are unavailable. Overall, the majority of tools and the consensus prediction lean toward pathogenicity, which is not contradicted by ClinVar (no entry) but is opposed by the AlphaMissense‑Optimized benign call. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.184	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign										0.247	Likely Benign	-3.12	Deleterious	0.876	Possibly Damaging	0.417	Benign	3.79	Benign	0.00	Affected			0.0767	0.5151		0	-1	3.3	16.06
c.454C>T	R152W 2D AIThe SynGAP1 missense variant R152W 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, 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		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.783	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.163	Likely Benign	-4.66	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.79	Benign	0.00	Affected			0.1550	0.4564		2	-3	3.6	30.03
c.470G>C	R157P 2D AIThe SynGAP1 missense variant R157P 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. 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 a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, 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		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-11.463	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.450	Likely Benign	-3.38	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.79	Benign	0.00	Affected			0.2438	0.3438		0	-2	2.9	-59.07
c.548A>C	H183P 2D AIThe SynGAP1 missense variant H183P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, 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 also predicts Pathogenic, while the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-18.527	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.410	Likely Benign	-7.18	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.79	Benign	0.01	Affected			0.2143	0.3712		0	-2	1.6	-40.02
c.548A>T	H183L 2D AIThe SynGAP1 missense variant H183L 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, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign votes). AlphaMissense‑Optimized alone also 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 to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-12.898	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.325	Likely Benign	-8.12	Deleterious	0.421	Benign	0.058	Benign	3.79	Benign	0.01	Affected			0.0911	0.5304		-2	-3	7.0	-23.98
c.622C>T	P208S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Rosetta’s output is uncertain and therefore not counted as evidence. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to pathogenic, and Foldetta also predicts pathogenic. With no ClinVar annotation to contradict, the overall evidence strongly favors a pathogenic classification for P208S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-8.363	Likely Pathogenic	0.587	Likely Pathogenic	Likely Benign	2.68	Destabilizing	0.3	1.53	Ambiguous	2.11	Destabilizing	1.21	Destabilizing	0.270	Likely Benign	-6.78	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.79	Benign	0.02	Affected			0.3808	0.4537		1	-1	0.8	-10.04
c.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.1216T>C	Y406H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y406H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently classify the substitution as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the preponderance of evidence indicates that Y406H is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-9.015	Likely Pathogenic	0.858	Likely Pathogenic	Ambiguous	2.13	Destabilizing	0.1	2.15	Destabilizing	2.14	Destabilizing	1.03	Destabilizing	0.239	Likely Benign	-4.21	Deleterious	0.997	Probably Damaging	0.966	Probably Damaging	3.80	Benign	0.03	Affected			0.2666	0.0811		0	2	-1.9	-26.03
c.1217A>C	Y406S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FoldX, Rosetta, premPS, and Foldetta all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-12.014	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	3.51	Destabilizing	0.3	4.08	Destabilizing	3.80	Destabilizing	1.40	Destabilizing	0.190	Likely Benign	-6.72	Deleterious	0.991	Probably Damaging	0.886	Possibly Damaging	3.80	Benign	0.06	Tolerated			0.4719	0.2817		-3	-2	0.5	-76.10
c.1457A>G	E486G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E486G missense change is not listed in ClinVar and has no gnomAD entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM. Those that predict a damaging outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-12.488	Likely Pathogenic	0.924	Likely Pathogenic	Ambiguous	1.09	Ambiguous	0.1	1.59	Ambiguous	1.34	Ambiguous	-0.14	Likely Benign	0.328	Likely Benign	-5.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.80	Benign	0.40	Tolerated			0.2918	0.5385		0	-2	3.1	-72.06
c.232C>T	R78C 2D AIThe SynGAP1 missense variant R78C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R78C, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-6.079	Likely Benign	0.467	Ambiguous	Likely Benign										0.114	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.194	Benign	3.80	Benign	0.00	Affected			0.3255	0.2804		-4	-3	7.0	-53.05
c.253A>C	T85P 2D AIThe SynGAP1 missense variant T85P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are not provided. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-8.406	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.28	Neutral	0.813	Possibly Damaging	0.053	Benign	3.80	Benign	0.00	Affected			0.1499	0.4485		0	-1	-0.9	-3.99
c.257T>C	V86A 2D AIThe SynGAP1 missense variant V86A has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Pathogenic predictions arise from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight a split: AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools (six benign vs. three pathogenic) suggest the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-3.022	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.059	Likely Benign	-1.35	Neutral	0.267	Benign	0.153	Benign	3.80	Benign	0.00	Affected			0.3205	0.2723		0	0	-2.4	-28.05
c.259T>A	S87T 2D AIThe SynGAP1 missense variant S87T is not reported 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, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-6.706	Likely Benign	0.776	Likely Pathogenic	Likely Benign										0.032	Likely Benign	-1.23	Neutral	0.140	Benign	0.153	Benign	3.80	Benign	0.00	Affected			0.1001	0.4708		1	1	0.1	14.03
c.469C>G	R157G 2D AIThe SynGAP1 R157G missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-9.125	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.252	Likely Benign	-3.52	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.80	Benign	0.00	Affected			0.3892	0.2567		-3	-2	4.1	-99.14
c.470G>A	R157H 2D AIThe SynGAP1 missense variant R157H (ClinVar ID 2065231.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33432767‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized 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, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the balance of predictions leans toward pathogenic, but the high‑accuracy tools do not provide a definitive verdict. This assessment does not contradict the ClinVar status, which remains Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.523978	Binding	0.306	0.777	0.375					Uncertain		1	6-33432767-G-A	1	6.20e-7	-10.235	Likely Pathogenic	0.604	Likely Pathogenic	Likely Benign										0.254	Likely Benign	-2.23	Neutral	0.999	Probably Damaging	0.987	Probably Damaging	3.80	Benign	0.00	Affected	3.74	4	0.2981	0.1449		2	0	1.3	-19.05
c.491G>T	R164L 2D AIThe SynGAP1 missense variant R164L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for R164L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250											-10.794	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous										0.274	Likely Benign	-3.37	Deleterious	0.001	Benign	0.003	Benign	3.80	Benign	0.00	Affected			0.2137	0.5154		-3	-2	8.3	-43.03
c.622C>G	P208A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P208A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Predictions that are inconclusive are 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 uncertain. Overall, the majority of evidence points toward 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	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-5.623	Likely Benign	0.172	Likely Benign	Likely Benign	2.19	Destabilizing	0.3	1.31	Ambiguous	1.75	Ambiguous	1.03	Destabilizing	0.245	Likely Benign	-6.80	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.80	Benign	0.04	Affected			0.3727	0.4390		1	-1	3.4	-26.04
c.165G>C	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			0.1352	0.4143		3	0	0.3	9.01
c.165G>T	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			0.1352	0.4143		3	0	0.3	9.01
c.2831G>C	G944A 2D AIThe SynGAP1 missense variant G944A is not reported 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		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750											-6.397	Likely Benign	0.089	Likely Benign	Likely Benign										0.314	Likely Benign	-0.61	Neutral	0.059	Benign	0.042	Benign	3.81	Benign	0.00	Affected			0.3352	0.4957		1	0	2.2	14.03
c.3218C>A	S1073Y 2D AIThe SynGAP1 missense change S1073Y 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; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-6.768	Likely Benign	0.752	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.43	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	3.81	Benign	0.00	Affected			0.0977	0.5684		-3	-2	-0.5	76.10
c.3218C>G	S1073C 2D AISynGAP1 missense variant S1073C is recorded in gnomAD (ID 6‑33443770‑C‑G) but has no ClinVar submission. Functional prediction tools show mixed results: benign calls come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The AlphaMissense‑Default score is uncertain. A consensus from the SGM framework (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because the votes are split. High‑accuracy methods give a benign prediction from AlphaMissense‑Optimized; the SGM Consensus remains ambiguous, and Foldetta stability analysis is unavailable. Consequently, the evidence does not strongly favor either outcome. The variant is most likely of uncertain significance, with no contradiction to ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750								6-33443770-C-G	1	6.23e-7	-8.862	Likely Pathogenic	0.461	Ambiguous	Likely Benign										0.137	Likely Benign	-1.52	Neutral	0.997	Probably Damaging	0.840	Possibly Damaging	3.81	Benign	0.00	Affected	3.77	5	0.1343	0.6088		-1	0	3.3	16.06
c.3218C>T	S1073F 2D AIThe SynGAP1 missense variant S1073F is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (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 impact. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-6.783	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.161	Likely Benign	-2.58	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	3.81	Benign	0.00	Affected			0.0952	0.5957		-3	-2	3.6	60.10
c.3235A>T	S1079C 2D AIThe SynGAP1 missense variant S1079C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive, and Foldetta data are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation, with four tools supporting pathogenicity versus three supporting benignity. 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.			0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-7.333	In-Between	0.370	Ambiguous	Likely Benign										0.138	Likely Benign	-2.61	Deleterious	0.898	Possibly Damaging	0.477	Possibly Damaging	3.81	Benign	0.00	Affected			0.0949	0.5536		0	-1	3.3	16.06
c.4013G>A	R1338Q 2D AIThe SynGAP1 missense variant R1338Q is listed in ClinVar (ID 450879.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451887‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which reports it as “Likely Benign.” In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000					Conflicting		3	6-33451887-G-A	12	8.40e-6	-3.494	Likely Benign	0.317	Likely Benign	Likely Benign										0.076	Likely Benign	-1.87	Neutral	0.896	Possibly Damaging	0.194	Benign	3.81	Benign	0.02	Affected	3.77	5	0.3528	0.2905		1	1	1.0	-28.06
c.401G>T	S134I 2D AIThe SynGAP1 missense variant S134I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as 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		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-8.860	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.27	Deleterious	0.041	Benign	0.031	Benign	3.81	Benign	0.00	Affected			0.0683	0.5191		-1	-2	5.3	26.08
c.463A>G	S155G 2D AIThe SynGAP1 missense variant S155G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically indicate a benign outcome from AlphaMissense‑Optimized, while SGM Consensus and Foldetta are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-9.243	Likely Pathogenic	0.628	Likely Pathogenic	Likely Benign										0.152	Likely Benign	-1.84	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.81	Benign	0.00	Affected			0.2416	0.3976		1	0	0.4	-30.03
c.464G>T	S155I 2D AIThe SynGAP1 missense variant S155I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and the Foldetta stability analysis is unavailable. Taken together, the majority of evidence points to a pathogenic impact for S155I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.298	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.70	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.81	Benign	0.00	Affected			0.0764	0.5711		-1	-2	5.3	26.08
c.470G>T	R157L 2D AIThe SynGAP1 missense variant R157L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-8.978	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-3.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.81	Benign	0.00	Affected			0.2015	0.3709		-3	-2	8.3	-43.03
c.538T>C	S180P 2D AIThe SynGAP1 missense variant S180P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-14.574	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-3.19	Deleterious	0.917	Possibly Damaging	0.446	Benign	3.81	Benign	0.01	Affected			0.1916	0.4735		1	-1	-0.8	10.04
c.547C>A	H183N 2D AIThe SynGAP1 H183N missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic impact are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of predictions, including the high‑accuracy tools, point to a pathogenic effect, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-12.028	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-4.97	Deleterious	0.012	Benign	0.006	Benign	3.81	Benign	0.01	Affected			0.1714	0.2589		2	1	-0.3	-23.04
c.547C>G	H183D 2D AIThe SynGAP1 missense variant H183D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized independently predicts Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of predictions (seven pathogenic vs. four benign) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for H183D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-18.626	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.311	Likely Benign	-6.55	Deleterious	0.421	Benign	0.107	Benign	3.81	Benign	0.01	Affected			0.2620	0.1817		1	-1	-0.3	-22.05
c.559C>G	L187V 2D AIThe SynGAP1 missense variant L187V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors lean toward a benign classification, but the single high‑accuracy tool indicates pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-10.543	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.136	Likely Benign	-2.24	Neutral	0.437	Benign	0.079	Benign	3.81	Benign	0.02	Affected			0.1525	0.3509		2	1	0.4	-14.03
c.572G>C	S191T 2D AIThe SynGAP1 missense variant S191T 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 majority‑vote SGM‑Consensus also classifies it as likely benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments corroborate the benign consensus: AlphaMissense‑Optimized returns a benign prediction and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports likely benign. Foldetta stability analysis is not available for this variant. Overall, the preponderance of evidence supports a benign classification, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.315	In-Between	0.319	Likely Benign	Likely Benign										0.150	Likely Benign	-2.34	Neutral	0.231	Benign	0.081	Benign	3.81	Benign	0.03	Affected			0.1466	0.7405		1	1	0.1	14.03
c.1136C>G	S379W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379W is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438041‑C‑G). Prediction tools that indicate a benign effect include premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus as benign. Because the majority of conventional tools favor pathogenicity while the high‑accuracy subset is split, the overall evidence leans toward a pathogenic effect. This conclusion does not contradict the ClinVar uncertain status, which remains unresolved. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625					Uncertain		1	6-33438041-C-G			-8.898	Likely Pathogenic	0.388	Ambiguous	Likely Benign	4.32	Destabilizing	3.4	3.56	Destabilizing	3.94	Destabilizing	0.16	Likely Benign	0.520	Likely Pathogenic	-1.02	Neutral	0.998	Probably Damaging	0.844	Possibly Damaging	3.82	Benign	0.01	Affected	4.32	11	0.1196	0.6070		-2	-3	-0.1	99.14	271.3	-75.7	1.4	1.0	0.6	0.5								Uncertain	Ser379 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 tryptophan are rarely tolerated. Although no major negative structural effects are observed in the variant simulations, Trp379 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effect on Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn
c.233G>C	R78P 2D AIThe SynGAP1 missense variant R78P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R78P, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-4.049	Likely Benign	0.611	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-1.72	Neutral	0.817	Possibly Damaging	0.123	Benign	3.82	Benign	0.00	Affected			0.2083	0.3750		0	-2	2.9	-59.07
c.254C>T	T85I 2D AIThe SynGAP1 missense variant T85I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized also predicts pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that T85I 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		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-9.310	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-2.50	Deleterious	0.813	Possibly Damaging	0.072	Benign	3.82	Benign	0.00	Affected			0.0634	0.5443		0	-1	5.2	12.05
c.317G>A	R106K 2D AIThe SynGAP1 missense variant R106K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for R106K, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-4.312	Likely Benign	0.513	Ambiguous	Likely Benign										0.150	Likely Benign	-1.25	Neutral	0.004	Benign	0.001	Benign	3.82	Benign	0.00	Affected			0.5602	0.4129	Weaken	3	2	0.6	-28.01
c.356A>G	E119G 2D AIThe SynGAP1 missense variant E119G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-4.349	Likely Benign	0.584	Likely Pathogenic	Likely Benign										0.143	Likely Benign	-2.40	Neutral	0.421	Benign	0.055	Benign	3.82	Benign	0.01	Affected			0.3246	0.6405		0	-2	3.1	-72.06
c.3968C>A	P1323Q 2D AIThe SynGAP1 missense variant P1323Q is reported in gnomAD (ID 6‑33451842‑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 predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that P1323Q is most likely benign, 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		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875								6-33451842-C-A			-6.134	Likely Benign	0.088	Likely Benign	Likely Benign										0.033	Likely Benign	-0.85	Neutral	0.712	Possibly Damaging	0.328	Benign	3.82	Benign	0.00	Affected	4.32	1	0.1791	0.4657		-1	0	-1.9	31.01
c.3968C>G	P1323R 2D AIThe SynGAP1 missense variant P1323R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that P1323R 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		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875											-5.785	Likely Benign	0.159	Likely Benign	Likely Benign										0.074	Likely Benign	-0.67	Neutral	0.002	Benign	0.003	Benign	3.82	Benign	0.00	Affected			0.1725	0.3015		0	-2	-2.9	59.07
c.3968C>T	P1323L 2D AIThe SynGAP1 missense variant P1323L is reported in gnomAD (variant ID 6‑33451842‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875								6-33451842-C-T	3	1.95e-6	-6.005	Likely Benign	0.084	Likely Benign	Likely Benign										0.045	Likely Benign	-1.04	Neutral	0.414	Benign	0.175	Benign	3.82	Benign	0.00	Affected	4.32	1	0.2650	0.6052		-3	-3	5.4	16.04
c.455G>C	R152P 2D AIThe SynGAP1 missense variant R152P 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 remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.499	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.332	Likely Benign	-4.00	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.82	Benign	0.00	Affected			0.2302	0.4838		0	-2	2.9	-59.07
c.476T>A	I159N 2D AIThe SynGAP1 missense variant I159N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑vs‑2 split. Foldetta, which would assess protein‑folding stability, has no available output for this variant. Overall, the majority of tools (five out of eight) predict pathogenicity, while three predict benign and one is uncertain. Thus, the variant is most likely pathogenic based on current computational predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-14.684	Likely Pathogenic	0.891	Likely Pathogenic	Ambiguous										0.218	Likely Benign	-1.93	Neutral	0.995	Probably Damaging	0.986	Probably Damaging	3.82	Benign	0.00	Affected			0.0919	0.0342		-2	-3	-8.0	0.94
c.491G>A	R164Q 2D AISynGAP1 missense variant R164Q is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33432788‑G‑A). Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are not available. Overall, the balance of evidence slightly favors a benign interpretation, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.512396	Binding	0.317	0.666	0.250					Uncertain		1	6-33432788-G-A	2	1.24e-6	-11.208	Likely Pathogenic	0.600	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.86	Neutral	0.957	Probably Damaging	0.342	Benign	3.82	Benign	0.00	Affected	3.74	4	0.3607	0.2711		1	1	1.0	-28.06
c.80C>G	P27R 2D AIThe SynGAP1 missense variant P27R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for P27R, 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											-3.260	Likely Benign	0.268	Likely Benign	Likely Benign										0.146	Likely Benign	-2.28	Neutral	0.972	Probably Damaging	0.954	Probably Damaging	3.82	Benign	0.00	Affected			0.1744	0.4203		0	-2	-2.9	59.07
c.80C>T	P27L 2D AIThe SynGAP1 missense variant P27L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-3.297	Likely Benign	0.161	Likely Benign	Likely Benign										0.174	Likely Benign	-2.59	Deleterious	0.909	Possibly Damaging	0.927	Probably Damaging	3.82	Benign	0.00	Affected			0.2684	0.6161		-3	-3	5.4	16.04
c.1135T>C	S379P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, Rosetta, and Foldetta; FoldX is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the majority of evidence—including the high‑accuracy benign predictions—suggests that the variant is most likely benign. 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	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625											-5.007	Likely Benign	0.118	Likely Benign	Likely Benign	1.10	Ambiguous	0.8	2.92	Destabilizing	2.01	Destabilizing	0.17	Likely Benign	0.430	Likely Benign	-0.41	Neutral	0.808	Possibly Damaging	0.212	Benign	3.83	Benign	0.10	Tolerated			0.3035	0.6594		1	-1	-0.8	10.04
c.1136C>T	S379L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379L is listed in ClinVar as Benign (ClinVar ID 1360860.0) and is present in gnomAD (ID 6‑33438041‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are Rosetta and SIFT. Foldetta and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence supports a benign impact, which is consistent with the ClinVar classification; there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625					Benign		1	6-33438041-C-T	8	4.05e-5	-5.641	Likely Benign	0.173	Likely Benign	Likely Benign	0.39	Likely Benign	0.2	3.38	Destabilizing	1.89	Ambiguous	-0.52	Ambiguous	0.469	Likely Benign	-0.85	Neutral	0.015	Benign	0.002	Benign	3.83	Benign	0.04	Affected	4.32	11	0.1891	0.5644		-3	-2	4.6	26.08	251.9	-48.1	0.6	1.1	0.0	0.5								Uncertain	Ser379 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 leucine are rarely tolerated. Although no negative structural effects are observed in the variant simulations, Leu379 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effect on Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.147C>G	C49W 2D AIThe SynGAP1 missense variant C49W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. 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). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic and the SGM‑Consensus is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that C49W 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		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-12.247	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.291	Likely Benign	-3.56	Deleterious	0.880	Possibly Damaging	0.914	Probably Damaging	3.83	Benign	0.00	Affected			0.1380	0.3172		-8	-2	-3.4	83.07
c.164A>C	Q55P 2D AIThe SynGAP1 missense variant Q55P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33423573‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign), and Foldetta results are unavailable. Overall, more tools predict pathogenicity than benignity, and no ClinVar entry contradicts this assessment. Therefore, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000								6-33423573-A-C	1	6.20e-7	-13.163	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.260	Likely Benign	-2.06	Neutral	0.462	Possibly Damaging	0.480	Possibly Damaging	3.83	Benign	0.00	Affected	4.32	1	0.2557	0.5508		-1	0	1.9	-31.01
c.164A>T	Q55L 2D AIThe SynGAP1 missense variant Q55L 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, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). 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		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.823	Likely Benign	0.844	Likely Pathogenic	Ambiguous										0.173	Likely Benign	-1.99	Neutral	0.273	Benign	0.275	Benign	3.83	Benign	0.00	Affected			0.0776	0.5982		-2	-2	7.3	-14.97
c.232C>G	R78G 2D AIThe SynGAP1 R78G missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign status: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Taken together, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-3.972	Likely Benign	0.480	Ambiguous	Likely Benign										0.072	Likely Benign	-1.94	Neutral	0.385	Benign	0.028	Benign	3.83	Benign	0.00	Affected			0.3285	0.2986		-3	-2	4.1	-99.14
c.233G>A	R78H 2D AIThe SynGAP1 R78H missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-4.851	Likely Benign	0.250	Likely Benign	Likely Benign										0.070	Likely Benign	-1.38	Neutral	0.908	Possibly Damaging	0.108	Benign	3.83	Benign	0.00	Affected			0.2453	0.1601		2	0	1.3	-19.05
c.2375A>T	E792V 2D AIThe SynGAP1 E792V missense change is not listed in ClinVar and has no allele record in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-4.643	Likely Benign	0.640	Likely Pathogenic	Likely Benign										0.072	Likely Benign	-3.85	Deleterious	0.000	Benign	0.001	Benign	3.83	Benign	0.00	Affected			0.0987	0.7772		-2	-2	7.7	-29.98
c.266C>G	P89R 2D AIThe SynGAP1 missense variant P89R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates 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.			0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-3.636	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.116	Likely Benign	-3.00	Deleterious	0.642	Possibly Damaging	0.097	Benign	3.83	Benign	0.00	Affected			0.1720	0.3362		0	-2	-2.9	59.07
c.3236G>T	S1079I 2D AIThe SynGAP1 missense variant S1079I is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (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 evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-4.732	Likely Benign	0.688	Likely Pathogenic	Likely Benign										0.093	Likely Benign	-2.86	Deleterious	0.078	Benign	0.025	Benign	3.83	Benign	0.00	Affected			0.0921	0.4775		-1	-2	5.3	26.08
c.353T>G	M118R 2D AIThe SynGAP1 missense variant M118R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized 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 balance of evidence leans toward a benign impact for M118R. This conclusion does not contradict any ClinVar annotation, as no ClinVar status is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-3.318	Likely Benign	0.698	Likely Pathogenic	Likely Benign										0.286	Likely Benign	-3.17	Deleterious	0.697	Possibly Damaging	0.202	Benign	3.83	Benign	0.00	Affected			0.2027	0.0913		0	-1	-6.4	24.99
c.454C>G	R152G 2D AIThe SynGAP1 missense variant R152G is not 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 score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R152G 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		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.043	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-4.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			0.3633	0.3956		-3	-2	4.1	-99.14
c.455G>T	R152L 2D AIThe SynGAP1 missense variant R152L 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, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that R152L 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		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.501	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.331	Likely Benign	-3.85	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			0.2032	0.5249		-3	-2	8.3	-43.03
c.533A>T	K178M 2D AIThe SynGAP1 missense variant K178M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-13.585	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-3.95	Deleterious	0.992	Probably Damaging	0.751	Possibly Damaging	3.83	Benign	0.00	Affected			0.1486	0.3607		0	-1	5.8	3.02
c.71T>C	V24A 2D AIThe SynGAP1 missense variant V24A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT predicts pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact for V24A. This prediction is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-2.980	Likely Benign	0.299	Likely Benign	Likely Benign										0.074	Likely Benign	-1.09	Neutral	0.000	Benign	0.001	Benign	3.83	Benign	0.00	Affected			0.3117	0.3350		0	0	-2.4	-28.05
c.233G>T	R78L 2D AIThe SynGAP1 missense variant R78L is listed in ClinVar (ID 3390541.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500					Uncertain		1				-3.389	Likely Benign	0.635	Likely Pathogenic	Likely Benign										0.062	Likely Benign	-1.59	Neutral	0.385	Benign	0.021	Benign	3.84	Benign	0.00	Affected			0.1445	0.4276		-3	-2	8.3	-43.03
c.259T>G	S87A 2D AIThe SynGAP1 missense variant S87A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (six benign predictions versus two pathogenic) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-7.817	In-Between	0.676	Likely Pathogenic	Likely Benign										0.039	Likely Benign	-1.24	Neutral	0.140	Benign	0.097	Benign	3.84	Benign	0.00	Affected			0.4272	0.3540		1	1	2.6	-16.00
c.272A>T	E91V 2D AIThe SynGAP1 E91V missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Overall, the evidence is mixed, but the consensus of several independent benign predictors and the SGM‑Consensus lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, 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		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-3.697	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-2.16	Neutral	0.947	Possibly Damaging	0.788	Possibly Damaging	3.84	Benign	0.00	Affected			0.0940	0.7457		-2	-2	7.7	-29.98
c.3233T>A	V1078D 2D AIThe SynGAP1 missense variant V1078D is listed in ClinVar (ID 2993122.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default, AlphaMissense‑Optimized, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the ClinVar “Uncertain” designation; there is no contradiction with the existing ClinVar status. 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					Uncertain		1				-5.155	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.158	Likely Benign	-1.45	Neutral	0.003	Benign	0.008	Benign	3.84	Benign	0.00	Affected	3.77	5	0.1570	0.1173		-3	-2	-7.7	15.96
c.353T>A	M118K 2D AIThe SynGAP1 missense variant M118K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, 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, as none exists for M118K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-3.979	Likely Benign	0.767	Likely Pathogenic	Likely Benign										0.276	Likely Benign	-2.98	Deleterious	0.396	Benign	0.099	Benign	3.84	Benign	0.01	Affected			0.2010	0.1131		0	-1	-5.8	-3.02
c.355G>C	E119Q 2D AIThe SynGAP1 missense variant E119Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments therefore favor a benign effect: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates that E119Q 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		0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-5.839	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.136	Likely Benign	-1.38	Neutral	0.596	Possibly Damaging	0.143	Benign	3.84	Benign	0.02	Affected			0.1627	0.7886		2	2	0.0	-0.98
c.356A>C	E119A 2D AIThe SynGAP1 missense variant E119A is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome; 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 balance of evidence (five benign versus three pathogenic predictions) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-4.881	Likely Benign	0.647	Likely Pathogenic	Likely Benign										0.108	Likely Benign	-2.52	Deleterious	0.231	Benign	0.074	Benign	3.84	Benign	0.01	Affected			0.4374	0.7514		0	-1	5.3	-58.04
c.400A>C	S134R 2D AIThe SynGAP1 missense variant S134R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as 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		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.400A>G	S134G 2D AIThe SynGAP1 missense variant S134G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors and the high‑accuracy consensus indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-6.722	Likely Benign	0.457	Ambiguous	Likely Benign										0.120	Likely Benign	-2.19	Neutral	0.034	Benign	0.035	Benign	3.84	Benign	0.00	Affected			0.2268	0.4008		1	0	0.4	-30.03
c.402C>A	S134R 2D AIThe SynGAP1 missense variant S134R 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the SGM‑Consensus remains 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		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.402C>G	S134R 2D AIThe SynGAP1 missense variant S134R 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the SGM‑Consensus remains 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		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.421A>C	I141L 2D AIThe SynGAP1 missense variant I141L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-6.563	Likely Benign	0.787	Likely Pathogenic	Ambiguous										0.156	Likely Benign	-1.00	Neutral	0.016	Benign	0.013	Benign	3.84	Benign	0.10	Tolerated			0.0742	0.3180		2	2	-0.7	0.00
c.430A>T	T144S 2D AIThe SynGAP1 missense variant T144S 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while 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, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for T144S. This conclusion does not contradict ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-7.730	In-Between	0.672	Likely Pathogenic	Likely Benign										0.081	Likely Benign	-1.90	Neutral	0.018	Benign	0.016	Benign	3.84	Benign	0.00	Affected			0.4039	0.4183		1	1	-0.1	-14.03
c.464G>A	S155N 2D AIThe SynGAP1 missense variant S155N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give mixed or unavailable results: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-9.428	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous										0.166	Likely Benign	-1.69	Neutral	0.981	Probably Damaging	0.954	Probably Damaging	3.84	Benign	0.00	Affected			0.1033	0.4549		1	1	-2.7	27.03
c.464G>C	S155T 2D AIThe SynGAP1 missense variant S155T is not 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, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of reliable predictors and the consensus analysis indicate that S155T is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-8.635	Likely Pathogenic	0.523	Ambiguous	Likely Benign										0.153	Likely Benign	-1.60	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.84	Benign	0.00	Affected			0.1151	0.5694		1	1	0.1	14.03
c.508C>T	R170W 2D AIThe SynGAP1 missense variant R170W is listed in ClinVar (ID 1310195.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250					Uncertain		2				-11.660	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.241	Likely Benign	-4.28	Deleterious	0.999	Probably Damaging	0.849	Possibly Damaging	3.84	Benign	0.00	Affected	3.74	4	0.1026	0.3469		2	-3	3.6	30.03
c.539C>T	S180L 2D AIThe SynGAP1 missense variant S180L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a “Likely Pathogenic” classification. AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic 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 Pathogenic		0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-12.967	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.250	Likely Benign	-3.80	Deleterious	0.608	Possibly Damaging	0.202	Benign	3.84	Benign	0.00	Affected			0.0885	0.5550		-3	-2	4.6	26.08
c.146G>A	C49Y 2D AIThe SynGAP1 missense variant C49Y 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 algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for C49Y. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-11.097	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous										0.312	Likely Benign	-3.38	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.85	Benign	0.00	Affected			0.1016	0.3172		0	-2	-3.8	60.04
c.188A>T	E63V 2D AIThe SynGAP1 E63V missense variant has no ClinVar record and is not present in gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Optimized returns an Uncertain result, and no Foldetta stability data are available. Overall, the balance of evidence leans toward a benign effect, with several high‑confidence predictors supporting pathogenicity, leaving the assessment inconclusive. The predictions do not contradict any ClinVar status, as none is assigned. Based on the aggregate predictions, the variant is most likely benign, and this 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		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.588	Likely Benign	0.921	Likely Pathogenic	Ambiguous										0.143	Likely Benign	-2.15	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	3.85	Benign	0.00	Affected			0.0559	0.7584		-2	-2	7.7	-29.98
c.256G>C	V86L 2D AIThe SynGAP1 missense variant V86L is reported in ClinVar as “not listed” and is present in the gnomAD database (ID 6‑33425864‑G‑C). 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, 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.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500								6-33425864-G-C	1	6.20e-7	-3.658	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.081	Likely Benign	-0.84	Neutral	0.267	Benign	0.097	Benign	3.85	Benign	0.00	Affected	4.32	1	0.1121	0.5386		1	2	-0.4	14.03
c.3210G>C	R1070S 2D AIThe SynGAP1 missense variant R1070S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-4.311	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-2.07	Neutral	0.789	Possibly Damaging	0.258	Benign	3.85	Benign	0.01	Affected			0.2640	0.4042		0	-1	3.7	-69.11
c.3210G>T	R1070S 2D AIThe SynGAP1 missense variant R1070S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-4.311	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-2.07	Neutral	0.789	Possibly Damaging	0.258	Benign	3.85	Benign	0.01	Affected			0.2640	0.4042		0	-1	3.7	-69.11
c.3217T>C	S1073P 2D AIThe SynGAP1 missense variant S1073P is reported in gnomAD (variant ID 6‑33443769‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for S1073P, 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		0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750								6-33443769-T-C	1	6.23e-7	-4.520	Likely Benign	0.338	Likely Benign	Likely Benign										0.082	Likely Benign	-0.76	Neutral	0.006	Benign	0.008	Benign	3.85	Benign	0.01	Affected	3.77	5	0.2243	0.5900		-1	1	-0.8	10.04
c.3233T>G	V1078G 2D AIThe SynGAP1 missense variant V1078G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign (3 benign vs 1 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence indicates a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750											-3.270	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.168	Likely Benign	-0.54	Neutral	0.157	Benign	0.292	Benign	3.85	Benign	0.00	Affected			0.2041	0.2693		-1	-3	-4.6	-42.08
c.355G>A	E119K 2D AIThe SynGAP1 missense variant E119K is not reported 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 FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. Overall, the majority of high‑accuracy predictors (including the SGM‑Consensus) indicate 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.	Likely Benign		0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-6.741	Likely Benign	0.922	Likely Pathogenic	Ambiguous										0.122	Likely Benign	-1.95	Neutral	0.012	Benign	0.006	Benign	3.85	Benign	0.01	Affected			0.2633	0.7739		0	1	-0.4	-0.94
c.401G>C	S134T 2D AIThe SynGAP1 missense variant S134T is listed in gnomAD (ID 6‑33432698‑G‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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 points to a benign impact; this conclusion is not contradicted by ClinVar, which contains no classification for S134T. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250								6-33432698-G-C	1	6.32e-7	-5.187	Likely Benign	0.563	Ambiguous	Likely Benign										0.069	Likely Benign	-1.76	Neutral	0.034	Benign	0.047	Benign	3.85	Benign	0.00	Affected	3.61	5	0.1083	0.5326		1	1	0.1	14.03
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.469C>A	R157S 2D AIThe SynGAP1 R157S missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic majority vote (2 pathogenic, 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R157S is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-7.573	In-Between	0.977	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-2.82	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.85	Benign	0.00	Affected			0.3484	0.2563		0	-1	3.7	-69.11
c.476T>G	I159S 2D AIThe SynGAP1 missense variant I159S is not 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 are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, 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 available predictions (five pathogenic vs. three benign) lean toward pathogenicity. 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.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-13.684	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-1.70	Neutral	0.995	Probably Damaging	0.979	Probably Damaging	3.85	Benign	0.00	Affected			0.2854	0.0712		-1	-2	-5.3	-26.08
c.478C>A	L160M 2D AIThe SynGAP1 missense variant L160M is not 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, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus is unavailable; and Foldetta, which combines FoldX‑MD and Rosetta stability calculations, has no reported output for this variant. Overall, the balance of evidence leans toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the lack of a ClinVar assertion mean the variant’s clinical significance remains uncertain. This assessment does not contradict any existing ClinVar status, as none is available. Thus, 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.			0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-11.120	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign										0.097	Likely Benign	-0.94	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	3.85	Benign	0.00	Affected			0.0837	0.3613		4	2	-1.9	18.03
c.79C>A	P27T 2D AIThe SynGAP1 missense variant P27T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including high‑accuracy tools, points to a benign effect for P27T, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-3.612	Likely Benign	0.103	Likely Benign	Likely Benign										0.106	Likely Benign	-2.07	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	3.85	Benign	0.00	Affected			0.2430	0.5923		0	-1	0.9	3.99
c.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.166C>A	L56M 2D AIThe SynGAP1 missense variant L56M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence (four benign versus three pathogenic predictions, with two uncertain) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has not been reported there. 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											-7.470	In-Between	0.345	Ambiguous	Likely Benign										0.109	Likely Benign	-0.51	Neutral	0.824	Possibly Damaging	0.910	Probably Damaging	3.86	Benign	0.00	Affected			0.0797	0.3574		4	2	-1.9	18.03
c.226T>G	S76A 2D AIThe SynGAP1 missense variant S76A is reported in gnomAD (ID 6‑33425834‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500								6-33425834-T-G	1	6.20e-7	-3.230	Likely Benign	0.072	Likely Benign	Likely Benign										0.048	Likely Benign	-1.10	Neutral	0.643	Possibly Damaging	0.277	Benign	3.86	Benign	0.00	Affected	4.32	1	0.4543	0.3619		1	1	2.6	-16.00
c.232C>A	R78S 2D AIThe SynGAP1 missense variant R78S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments are: AlphaMissense‑Optimized (Uncertain), SGM‑Consensus (Likely Benign), and Foldetta (no data available). Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-3.680	Likely Benign	0.792	Likely Pathogenic	Ambiguous										0.063	Likely Benign	-1.11	Neutral	0.385	Benign	0.015	Benign	3.86	Benign	0.00	Affected			0.3081	0.3274		0	-1	3.7	-69.11
c.239A>T	K80I 2D AIThe SynGAP1 missense variant K80I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic signals and no ClinVar entry to contradict the computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.320	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.083	Likely Benign	-2.54	Deleterious	0.939	Possibly Damaging	0.164	Benign	3.86	Benign	0.00	Affected			0.1095	0.2981		-2	-3	8.4	-15.01
c.272A>G	E91G 2D AIThe SynGAP1 missense variant E91G is listed in ClinVar (ID 436922.0) as benign 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 (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 classifying the variant as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicating a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, 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		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500					Likely Benign		1				-3.226	Likely Benign	0.783	Likely Pathogenic	Likely Benign										0.110	Likely Benign	-2.18	Neutral	0.947	Possibly Damaging	0.727	Possibly Damaging	3.86	Benign	0.00	Affected	4.32	1	0.3418	0.6030		0	-2	3.1	-72.06
c.3209G>A	R1070K 2D AIThe SynGAP1 missense variant R1070K is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy tools reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta results are unavailable. Based on the unanimous benign predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875					Conflicting		2				-5.093	Likely Benign	0.326	Likely Benign	Likely Benign										0.104	Likely Benign	-1.42	Neutral	0.049	Benign	0.048	Benign	3.86	Benign	0.09	Tolerated	3.77	5	0.4997	0.4867		3	2	0.6	-28.01
c.3235A>C	S1079R 2D AIThe SynGAP1 missense variant S1079R 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, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.3237C>A	S1079R 2D AIThe SynGAP1 missense variant S1079R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33443789‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is inconclusive. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments are limited: AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750					Uncertain		1	6-33443789-C-A	4	2.51e-6	-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.3237C>G	S1079R 2D AIThe SynGAP1 missense variant S1079R is listed in ClinVar (ID 1047537.0) as Benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta (FoldX‑MD/Rosetta stability) result is available. High‑accuracy assessments therefore show a benign consensus (SGM‑Consensus) with one uncertain AlphaMissense‑Optimized prediction and no destabilizing Foldetta evidence. Overall, the majority of predictions support a benign classification, which is consistent with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750					Benign		1				-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.353T>C	M118T 2D AIThe SynGAP1 missense variant M118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) also indicates a likely benign classification, and AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the evidence from multiple independent predictors and the high‑accuracy consensus strongly supports a benign impact. This conclusion is consistent with the lack of any ClinVar pathogenic annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-2.468	Likely Benign	0.454	Ambiguous	Likely Benign										0.217	Likely Benign	-2.41	Neutral	0.396	Benign	0.067	Benign	3.86	Benign	0.08	Tolerated			0.2207	0.2237		-1	-1	-2.6	-30.09
c.451G>C	D151H 2D AIThe SynGAP1 missense variant D151H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33432748‑G‑C). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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 result is available for this variant. Overall, the majority of computational evidence indicates that D151H is most likely pathogenic, which does not contradict the current ClinVar status of uncertainty. 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					Uncertain		1	6-33432748-G-C	2	1.26e-6	-11.747	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.335	Likely Benign	-3.90	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	3.86	Benign	0.00	Affected	3.61	5	0.1543	0.8419		-1	1	0.3	22.05
c.476T>C	I159T 2D AIThe SynGAP1 missense variant I159T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect comprise polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while AlphaMissense‑Default also predicts pathogenic. Given that six of the seven individual tools predict pathogenicity versus three predicting benign, the variant is most likely pathogenic. This prediction does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-12.422	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.218	Likely Benign	-1.69	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.86	Benign	0.00	Affected			0.1069	0.0685		0	-1	-5.2	-12.05
c.479T>C	L160P 2D AIThe SynGAP1 missense variant L160P 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. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. 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											-15.939	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.283	Likely Benign	-3.06	Deleterious	0.001	Benign	0.000	Benign	3.86	Benign	0.00	Affected			0.3589	0.1484		-3	-3	-5.4	-16.04
c.509G>C	R170P 2D AIThe SynGAP1 missense variant R170P is not 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 score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R170P 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		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-9.687	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.386	Likely Benign	-3.96	Deleterious	0.966	Probably Damaging	0.599	Possibly Damaging	3.86	Benign	0.00	Affected			0.1967	0.3989		0	-2	2.9	-59.07
c.533A>C	K178T 2D AIThe SynGAP1 missense variant K178T is not reported in ClinVar and is absent from gnomAD. Computational predictors show a split: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-13.359	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.249	Likely Benign	-3.95	Deleterious	0.759	Possibly Damaging	0.306	Benign	3.86	Benign	0.01	Affected			0.2631	0.2788		0	-1	3.2	-27.07
c.534G>C	K178N 2D AIThe SynGAP1 missense variant K178N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus reports Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions, K178N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.534G>T	K178N 2D AIThe SynGAP1 missense variant K178N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.538T>A	S180T 2D AIThe SynGAP1 missense variant S180T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) support a benign classification. This consensus does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Thus, the variant is most likely benign based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-9.851	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign										0.114	Likely Benign	-2.07	Neutral	0.057	Benign	0.020	Benign	3.86	Benign	0.02	Affected			0.1238	0.5171		1	1	0.1	14.03
c.1135T>A	S379T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are Rosetta, polyPhen‑2 HumDiv, and the Foldetta stability method. FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625											-5.646	Likely Benign	0.092	Likely Benign	Likely Benign	1.42	Ambiguous	0.6	3.96	Destabilizing	2.69	Destabilizing	0.06	Likely Benign	0.230	Likely Benign	-0.50	Neutral	0.462	Possibly Damaging	0.084	Benign	3.87	Benign	0.16	Tolerated			0.2293	0.6248		1	1	0.1	14.03
c.145T>G	C49G 2D AIThe SynGAP1 missense variant C49G is not 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. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.464	Likely Benign	0.674	Likely Pathogenic	Likely Benign										0.351	Likely Benign	-3.64	Deleterious	0.462	Possibly Damaging	0.599	Possibly Damaging	3.87	Benign	0.00	Affected			0.2419	0.2528		-3	-3	-2.9	-46.09
c.164A>G	Q55R 2D AIThe SynGAP1 missense variant Q55R is not reported 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 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 (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 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.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-6.626	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.166	Likely Benign	-1.15	Neutral	0.140	Benign	0.275	Benign	3.87	Benign	0.00	Affected			0.1607	0.1558		1	1	-1.0	28.06
c.188A>G	E63G 2D AIThe SynGAP1 missense variant E63G is not reported 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, reports the variant as Likely Benign. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Overall, the majority of individual predictors and the SGM‑Consensus lean toward a benign interpretation, with no conflicting evidence from ClinVar. Thus, the variant is most likely benign based on current computational predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.450	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-2.24	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	3.87	Benign	0.00	Affected			0.2705	0.5786		0	-2	3.1	-72.06
c.2060G>C	R687P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R687P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas the remaining eleven tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—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, and PROVEAN) reports a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no conflicting ClinVar annotation, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-15.697	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.31	Destabilizing	0.3	6.63	Destabilizing	4.47	Destabilizing	0.89	Ambiguous	0.553	Likely Pathogenic	-6.12	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.87	Benign	0.01	Affected			0.1811	0.3159		0	-2	2.9	-59.07
c.253A>T	T85S 2D AIThe SynGAP1 missense variant T85S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of conventional predictors lean toward a benign impact, but the high‑accuracy AlphaMissense‑Optimized tool suggests pathogenicity, creating a conflict. No ClinVar entry exists, so there is no reported status to contradict. Based on the collective evidence, the variant is most likely benign, though the high‑accuracy prediction indicates uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-4.171	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.103	Likely Benign	-1.37	Neutral	0.113	Benign	0.011	Benign	3.87	Benign	0.00	Affected			0.2590	0.3569		1	1	-0.1	-14.03
c.2941G>A	G981S 2D AIThe SynGAP1 missense variant G981S 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is not available for this variant. Overall, the majority of evidence—including the consensus and high‑accuracy tools—points to a benign effect. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625											-2.749	Likely Benign	0.274	Likely Benign	Likely Benign										0.130	Likely Benign	-0.57	Neutral	0.979	Probably Damaging	0.907	Possibly Damaging	3.87	Benign	0.00	Affected			0.2566	0.5470		1	0	-0.4	30.03
c.2944T>G	Y982D 2D AIThe SynGAP1 missense variant Y982D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-5.021	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-1.29	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	3.87	Benign	0.00	Affected			0.3959	0.0545		-4	-3	-2.2	-48.09
c.2945A>G	Y982C 2D AIThe SynGAP1 missense variant Y982C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443497‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625					Conflicting		2	6-33443497-A-G	2	1.24e-6	-6.256	Likely Benign	0.746	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-1.67	Neutral	0.997	Probably Damaging	0.923	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.2988	0.2345		0	-2	3.8	-60.04
c.31G>T	G11W 2D AIThe SynGAP1 missense variant G11W is catalogued in gnomAD (ID 6‑33420295‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from 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; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is reported). 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								6-33420295-G-T			-5.819	Likely Benign	0.403	Ambiguous	Likely Benign										0.096	Likely Benign	-0.67	Neutral	0.959	Probably Damaging	0.318	Benign	3.87	Benign	0.00	Affected	4.32	1	0.0747	0.4731		-2	-7	-0.5	129.16
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.3235A>G	S1079G 2D AIThe SynGAP1 missense variant S1079G is reported in gnomAD (variant ID 6‑33443787‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750								6-33443787-A-G	6	3.76e-6	-3.552	Likely Benign	0.177	Likely Benign	Likely Benign										0.065	Likely Benign	-1.50	Neutral	0.036	Benign	0.018	Benign	3.87	Benign	0.00	Affected	3.77	5	0.2151	0.4623		0	1	0.4	-30.03
c.440A>C	Q147P 2D AIThe SynGAP1 missense variant Q147P is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the balance of evidence, especially the SGM Consensus and the majority of individual predictors, indicates that 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		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-14.132	Likely Pathogenic	0.797	Likely Pathogenic	Ambiguous										0.264	Likely Benign	-3.03	Deleterious	0.232	Benign	0.147	Benign	3.87	Benign	0.01	Affected			0.2350	0.4402		0	-1	1.9	-31.01
c.441A>C	Q147H 2D AIThe SynGAP1 missense variant Q147H is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the balance of evidence, especially the SGM Consensus and the majority of individual predictors, indicates that 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		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.759	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.102	Likely Benign	-2.70	Deleterious	0.380	Benign	0.265	Benign	3.87	Benign	0.01	Affected			0.1528	0.3220		3	0	0.3	9.01
c.441A>T	Q147H 2D AIThe SynGAP1 missense variant Q147H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.759	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.102	Likely Benign	-2.70	Deleterious	0.380	Benign	0.265	Benign	3.87	Benign	0.01	Affected			0.1528	0.3220		3	0	0.3	9.01
c.452A>G	D151G 2D AIThe SynGAP1 D151G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and FATHMM, whereas the remaining eight tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence indicates that D151G is most likely pathogenic, and this assessment does not conflict with any ClinVar annotation, as none exists. 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											-10.409	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.349	Likely Benign	-3.91	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.87	Benign	0.01	Affected			0.4452	0.7037		1	-1	3.1	-58.04
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.479T>A	L160Q 2D AIThe SynGAP1 missense variant L160Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-16.626	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-2.83	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.87	Benign	0.00	Affected			0.1248	0.1060		-2	-2	-7.3	14.97
c.509G>T	R170L 2D AIThe SynGAP1 missense variant R170L has no ClinVar entry and is not reported in gnomAD. In silico predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (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 preponderance of pathogenic predictions, including the high‑accuracy consensus, suggests that R170L is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-8.649	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-4.02	Deleterious	0.798	Possibly Damaging	0.319	Benign	3.87	Benign	0.00	Affected			0.1561	0.4310		-3	-2	8.3	-43.03
c.562A>T	S188C 2D AIThe SynGAP1 missense variant S188C is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default, all of which classify the substitution as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, while Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-8.670	Likely Pathogenic	0.849	Likely Pathogenic	Ambiguous										0.111	Likely Benign	-2.96	Deleterious	0.999	Probably Damaging	0.956	Probably Damaging	3.87	Benign	0.00	Affected			0.1007	0.6737		0	-1	3.3	16.06
c.76G>A	G26R 2D AIThe SynGAP1 missense variant G26R is listed in ClinVar as a benign alteration (ClinVar ID 1521495.0) and is present in the gnomAD database (gnomAD ID 6‑33423485‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence supports a benign impact, aligning with the ClinVar designation and indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375					Benign		1	6-33423485-G-A	3	1.86e-6	-2.946	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.22	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.1097	0.4407		-3	-2	-4.1	99.14
c.76G>C	G26R 2D AIThe SynGAP1 missense variant G26R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of the four high‑accuracy tools) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy consensus—indicates that G26R is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375											-2.946	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.22	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.1097	0.4407		-3	-2	-4.1	99.14
c.1220A>C	Q407P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; premPS is uncertain and is not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of these 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	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-13.578	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.04	Destabilizing	0.5	2.07	Destabilizing	2.56	Destabilizing	0.88	Ambiguous	0.515	Likely Pathogenic	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.88	Benign	0.02	Affected			0.1786	0.4352		0	-1	1.9	-31.01
c.1221G>C	Q407H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407H (C2 domain) has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain. No evidence from FoldX, Rosetta, or Foldetta supports a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.1221G>T	Q407H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q407H is listed in ClinVar with an uncertain significance (ClinVar ID 2772184.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked as uncertain include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Q407H. This conclusion does not conflict with the ClinVar designation of uncertain significance, which remains unresolved pending further evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000					Uncertain		1				-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.2059C>G	R687G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R687G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta indicates a destabilizing, pathogenic effect. AlphaMissense‑Optimized is uncertain and therefore treated as unavailable. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, 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	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-12.900	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	2.94	Destabilizing	0.3	2.53	Destabilizing	2.74	Destabilizing	1.27	Destabilizing	0.360	Likely Benign	-6.26	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.88	Benign	0.01	Affected			0.2508	0.2119		-3	-2	4.1	-99.14
c.2375A>G	E792G 2D AIThe SynGAP1 E792G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic vote). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta results are unavailable. Overall, the consensus of available predictions indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.925	Likely Benign	0.353	Ambiguous	Likely Benign										0.037	Likely Benign	-3.77	Deleterious	0.000	Benign	0.000	Benign	3.88	Benign	0.01	Affected			0.3145	0.6036		0	-2	3.1	-72.06
c.253A>G	T85A 2D AIThe SynGAP1 missense variant T85A is not reported in ClinVar and is absent from gnomAD. Consensus and most in‑silico predictors classify it as benign: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all indicate a benign effect. In contrast, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic impact. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized reports a pathogenic change, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools and the consensus prediction lean toward a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-4.803	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.101	Likely Benign	-1.79	Neutral	0.060	Benign	0.004	Benign	3.88	Benign	0.00	Affected			0.3155	0.3517		1	0	2.5	-30.03
c.254C>A	T85K 2D AIThe SynGAP1 missense variant T85K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields an equal split (2 pathogenic, 2 benign) and is therefore considered unavailable; Foldetta results are not provided and are likewise unavailable. Overall, the majority of available predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-9.278	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.127	Likely Benign	-2.32	Neutral	0.588	Possibly Damaging	0.036	Benign	3.88	Benign	0.00	Affected			0.0823	0.2796		0	-1	-3.2	27.07
c.2944T>A	Y982N 2D AIThe SynGAP1 Y982N variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is benign, and Foldetta results are unavailable. Overall, the majority of consensus‑based and high‑accuracy tools lean toward a benign interpretation. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar status, which currently has no entry for Y982N. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-4.536	Likely Benign	0.881	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-1.14	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	3.88	Benign	0.00	Affected			0.2090	0.0545		-2	-2	-2.2	-49.07
c.3215A>T	K1072M 2D AIThe SynGAP1 K1072M 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, 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		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.821	Likely Benign	0.928	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-1.37	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.88	Benign	0.02	Affected			0.1266	0.4877		0	-1	5.8	3.02
c.377T>G	F126C 2D AIThe SynGAP1 missense variant F126C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools 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.			0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-2.553	Likely Benign	0.824	Likely Pathogenic	Ambiguous										0.109	Likely Benign	-3.19	Deleterious	0.952	Possibly Damaging	0.570	Possibly Damaging	3.88	Benign	0.00	Affected			0.2682	0.1270		-4	-2	-0.3	-44.04
c.379C>T	R127W 2D AISynGAP1 missense variant R127W is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Consequently, the evidence does not favor a clear benign or pathogenic outcome; the predictions are balanced and align with the ClinVar designation of Uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.711716	Binding	0.333	0.870	0.625					Uncertain		1				-4.776	Likely Benign	0.806	Likely Pathogenic	Ambiguous										0.118	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.420	Benign	3.88	Benign	0.00	Affected			0.1583	0.3005		2	-3	3.6	30.03
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.3967C>T	P1323S 2D AIThe SynGAP1 missense variant P1323S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875											-6.007	Likely Benign	0.072	Likely Benign	Likely Benign										0.077	Likely Benign	-0.52	Neutral	0.588	Possibly Damaging	0.122	Benign	3.88	Benign	0.00	Affected			0.3758	0.4371		1	-1	0.8	-10.04
c.452A>T	D151V 2D AIThe SynGAP1 D151V 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 and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151V 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											-11.927	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.380	Likely Benign	-5.19	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.88	Benign	0.00	Affected			0.0864	0.7781		-2	-3	7.7	-15.96
c.463A>C	S155R 2D AIThe SynGAP1 missense variant S155R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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 evidence from both general and high‑accuracy predictors indicates that the S155R 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		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.939	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.250	Likely Benign	-2.74	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	3.88	Benign	0.00	Affected			0.0712	0.3528		0	-1	-3.7	69.11
c.465C>A	S155R 2D AIThe SynGAP1 missense variant S155R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and a Foldetta stability analysis is not available. Taken together, the majority of evidence points to a pathogenic impact for S155R. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.939	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.160	Likely Benign	-2.74	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	3.88	Benign	0.00	Affected			0.0712	0.3528		0	-1	-3.7	69.11
c.465C>G	S155R 2D AIThe SynGAP1 missense variant S155R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and a Foldetta stability analysis is not available. Taken together, the majority of evidence points to a pathogenic impact for S155R. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.939	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.160	Likely Benign	-2.74	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	3.88	Benign	0.00	Affected			0.0712	0.3528		0	-1	-3.7	69.11
c.508C>G	R170G 2D AIThe SynGAP1 missense variant R170G is not reported in ClinVar and has no entries in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact for R170G, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-10.092	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-3.19	Deleterious	0.664	Possibly Damaging	0.137	Benign	3.88	Benign	0.00	Affected			0.3285	0.3004		-3	-2	4.1	-99.14
c.532A>C	K178Q 2D AIThe SynGAP1 K178Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-9.779	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-2.57	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.88	Benign	0.01	Affected			0.5170	0.1216	Weaken	1	1	0.4	-0.04
c.549T>A	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.549T>G	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.110C>G	S37C 2D AIThe SynGAP1 missense variant S37C 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		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-4.304	Likely Benign	0.141	Likely Benign	Likely Benign										0.116	Likely Benign	-1.18	Neutral	0.880	Possibly Damaging	0.923	Probably Damaging	3.89	Benign	0.00	Affected			0.1623	0.5775		0	-1	3.3	16.06
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.163C>G	Q55E 2D AIThe SynGAP1 missense variant Q55E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while SIFT uniquely predicts pathogenic. ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also indicates 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		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-7.361	In-Between	0.265	Likely Benign	Likely Benign										0.052	Likely Benign	-0.98	Neutral	0.064	Benign	0.184	Benign	3.89	Benign	0.00	Affected			0.1380	0.2632		2	2	0.0	0.98
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.2374G>C	E792Q 2D AIThe SynGAP1 missense variant E792Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” verdict, reflecting the majority of benign calls. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E792Q is most likely benign, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.782	Likely Benign	0.411	Ambiguous	Likely Benign										0.052	Likely Benign	-1.60	Neutral	0.077	Benign	0.049	Benign	3.89	Benign	0.02	Affected			0.1469	0.7401		2	2	0.0	-0.98
c.239A>C	K80T 2D AIThe SynGAP1 missense variant K80T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized prediction is uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-4.987	Likely Benign	0.830	Likely Pathogenic	Ambiguous										0.072	Likely Benign	-1.60	Neutral	0.588	Possibly Damaging	0.036	Benign	3.89	Benign	0.00	Affected			0.2139	0.2321		0	-1	3.2	-27.07
c.240A>C	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.240A>T	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.2582C>G	S861W 2D AIThe SynGAP1 missense variant S861W has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority of the four high‑accuracy tools) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-8.538	Likely Pathogenic	0.585	Likely Pathogenic	Likely Benign										0.267	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	3.89	Benign	0.01	Affected			0.0874	0.6247		-2	-3	-0.1	99.14
c.271G>C	E91Q 2D AIThe SynGAP1 missense variant E91Q has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Overall, the predictions are mixed, with an equal number of benign and pathogenic calls, but the consensus‑based SGM‑Consensus and the majority of individual benign predictions lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-4.053	Likely Benign	0.805	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-0.89	Neutral	0.947	Possibly Damaging	0.727	Possibly Damaging	3.89	Benign	0.00	Affected			0.1487	0.7442		2	2	0.0	-0.98
c.272A>C	E91A 2D AIThe SynGAP1 missense variant E91A is not reported 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 agree on 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, reports the variant as Likely Benign. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. Overall, the majority of consensus‑based and individual predictors lean toward a benign classification, with several high‑confidence tools indicating pathogenicity, leaving the assessment inconclusive. Based on the available predictions, the variant is most likely benign, 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 Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-3.302	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.094	Likely Benign	-1.58	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.89	Benign	0.00	Affected			0.4511	0.7077		0	-1	5.3	-58.04
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.2945A>C	Y982S 2D AIThe SynGAP1 missense variant Y982S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus as Likely Benign, AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-2.919	Likely Benign	0.841	Likely Pathogenic	Ambiguous										0.131	Likely Benign	-1.04	Neutral	0.965	Probably Damaging	0.783	Possibly Damaging	3.89	Benign	0.00	Affected			0.4556	0.1883		-3	-2	0.5	-76.10
c.455G>A	R152Q 2D AIThe SynGAP1 missense variant R152Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33432752‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus remains unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result for this variant. Overall, the preponderance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625					Uncertain		1	6-33432752-G-A	5	3.14e-6	-10.336	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-2.34	Neutral	0.997	Probably Damaging	0.968	Probably Damaging	3.89	Benign	0.00	Affected	3.61	5	0.3618	0.2996		1	1	1.0	-28.06
c.477C>G	I159M 2D AIThe SynGAP1 missense variant I159M is not reported 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 (majority vote) which classifies the variant as 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. 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		0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-9.838	Likely Pathogenic	0.142	Likely Benign	Likely Benign										0.071	Likely Benign	-0.48	Neutral	0.995	Probably Damaging	0.986	Probably Damaging	3.89	Benign	0.00	Affected			0.0678	0.2500		2	1	-2.6	18.03
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.631A>T	S211C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and premPS, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Two tools (Rosetta and AlphaMissense‑Default) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Because the consensus of the most reliable predictors is split (two benign, one pathogenic) and the overall tool distribution is evenly divided, the variant’s impact remains ambiguous. Based on the available predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-10.567	Likely Pathogenic	0.547	Ambiguous	Likely Benign	0.28	Likely Benign	0.1	0.63	Ambiguous	0.46	Likely Benign	0.11	Likely Benign	0.263	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.908	Possibly Damaging	3.89	Benign	0.01	Affected			0.1292	0.5638		0	-1	3.3	16.06
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.89A>C	H30P 2D AIThe SynGAP1 H30P missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-1.933	Likely Benign	0.077	Likely Benign	Likely Benign										0.202	Likely Benign	-2.77	Deleterious	0.676	Possibly Damaging	0.599	Possibly Damaging	3.89	Benign	0.00	Affected			0.2527	0.4723		0	-2	1.6	-40.02
c.109T>C	S37P 2D AIThe SynGAP1 missense variant S37P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for S37P, 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		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-3.788	Likely Benign	0.149	Likely Benign	Likely Benign										0.156	Likely Benign	-1.29	Neutral	0.676	Possibly Damaging	0.693	Possibly Damaging	3.90	Benign	0.00	Affected			0.2657	0.5327		1	-1	-0.8	10.04
c.110C>A	S37Y 2D AIThe SynGAP1 missense variant S37Y is listed in gnomAD (ID 6‑33423519‑C‑A) 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, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no available result. High‑accuracy assessments 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. 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		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500								6-33423519-C-A	1	6.20e-7	-4.447	Likely Benign	0.370	Ambiguous	Likely Benign										0.132	Likely Benign	-1.61	Neutral	0.880	Possibly Damaging	0.888	Possibly Damaging	3.90	Benign	0.00	Affected	4.32	1	0.1247	0.5256		-2	-3	-0.5	76.10
c.110C>T	S37F 2D AIThe SynGAP1 missense variant S37F 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		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-4.258	Likely Benign	0.412	Ambiguous	Likely Benign										0.131	Likely Benign	-1.77	Neutral	0.676	Possibly Damaging	0.828	Possibly Damaging	3.90	Benign	0.00	Affected			0.1060	0.5552		-3	-2	3.6	60.10
c.1117G>A	G373R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G373R is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438022‑G‑A). Prediction tools that classify the variant as benign include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized, and premPS. Those that predict pathogenicity are REVEL, FoldX, Foldetta, SIFT, 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 pathogenic. No prediction or folding result is missing or inconclusive. Overall, the majority of tools (six versus five) and the consensus of high‑accuracy methods lean toward a benign effect. 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.		C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625								6-33438022-G-A	1	6.28e-7	-7.878	In-Between	0.653	Likely Pathogenic	Likely Benign	4.28	Destabilizing	3.5	0.14	Likely Benign	2.21	Destabilizing	0.21	Likely Benign	0.510	Likely Pathogenic	-0.64	Neutral	0.001	Benign	0.000	Benign	3.90	Benign	0.01	Affected	3.53	16	0.1089	0.4524		-2	-3	-4.1	99.14
c.1117G>C	G373R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G373R is 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, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, Foldetta, SIFT, and AlphaMissense‑Default; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as pathogenic. Overall, the majority of tools (seven benign vs five pathogenic) lean toward a benign interpretation, and this does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625											-7.878	In-Between	0.653	Likely Pathogenic	Likely Benign	4.28	Destabilizing	3.5	0.14	Likely Benign	2.21	Destabilizing	0.21	Likely Benign	0.522	Likely Pathogenic	-0.64	Neutral	0.001	Benign	0.000	Benign	3.90	Benign	0.01	Affected	3.53	16	0.1089	0.4524		-2	-3	-4.1	99.14
c.1118G>A	G373E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G373E is listed in ClinVar with an Uncertain significance and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, Foldetta, SIFT, and AlphaMissense‑Default. Predictions from Rosetta and ESM1b are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as pathogenic. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625					Uncertain		1				-7.281	In-Between	0.569	Likely Pathogenic	Likely Benign	4.13	Destabilizing	3.2	0.52	Ambiguous	2.33	Destabilizing	-0.02	Likely Benign	0.420	Likely Benign	-0.69	Neutral	0.001	Benign	0.000	Benign	3.90	Benign	0.01	Affected			0.1572	0.4309		0	-2	-3.1	72.06
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.1156G>T	G386W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G386W is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Computational predictors that classify the change as benign include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. High‑accuracy assessments give a benign verdict from AlphaMissense‑Optimized, a benign consensus from the SGM method (majority of the four contributing tools are benign), and a pathogenic result from Foldetta. Uncertain calls from AlphaMissense‑Default and Rosetta are treated as unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750											-10.389	Likely Pathogenic	0.519	Ambiguous	Likely Benign	6.07	Destabilizing	5.5	1.28	Ambiguous	3.68	Destabilizing	-0.23	Likely Benign	0.471	Likely Benign	-0.85	Neutral	0.996	Probably Damaging	0.920	Probably Damaging	3.90	Benign	0.00	Affected			0.1058	0.4676		-7	-2	-0.5	129.16
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.1231A>G	I411V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411V is reported in ClinVar as benign (ClinVar ID 1654508.0) and is not found in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a pathogenic outcome: PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are AlphaMissense‑Default, FoldX, Rosetta, premPS, and Foldetta. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. Overall, the preponderance of evidence points to a benign effect for I411V, which is consistent with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000					Likely Benign		1				-6.290	Likely Benign	0.385	Ambiguous	Likely Benign	0.74	Ambiguous	0.0	0.82	Ambiguous	0.78	Ambiguous	0.99	Ambiguous	0.212	Likely Benign	-0.86	Neutral	0.935	Possibly Damaging	0.858	Possibly Damaging	3.90	Benign	0.27	Tolerated	3.38	28	0.1112	0.3526		4	3	-0.3	-14.03	233.3	28.2	-0.2	0.0	-0.2	0.0						X		Potentially Benign	The sec-butyl side chain of Ile411, located in the hydrophobic space between an anti-parallel β sheet strand (res. Pro398-Ile411) and an α helix (res. Asp684-Gln702), packs against multiple residues (e.g., Met409, Arg259). In the variant simulations, the side chain of Val411 is able to favorably fill the same hydrophobic niche despite its slightly smaller size. In short, the residue swap has no apparent negative effect on the structure based on the simulations.
c.166C>G	L56V 2D AIThe SynGAP1 missense variant L56V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs 1 pathogenic, 1 uncertain). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the L56V variant, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-8.104	Likely Pathogenic	0.471	Ambiguous	Likely Benign										0.123	Likely Benign	-0.99	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.90	Benign	0.00	Affected			0.1635	0.3655		2	1	0.4	-14.03
c.170T>A	L57H 2D AIThe SynGAP1 missense variant L57H is not reported in ClinVar and has no entry in gnomAD. Prediction tools show a split: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further indicate that AlphaMissense‑Optimized is Uncertain, whereas the SGM‑Consensus remains Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of high‑confidence tools and the consensus score favor 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		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-6.251	Likely Benign	0.796	Likely Pathogenic	Ambiguous										0.173	Likely Benign	-1.58	Neutral	0.984	Probably Damaging	0.971	Probably Damaging	3.90	Benign	0.00	Affected			0.1045	0.0611		-2	-3	-7.0	23.98
c.170T>C	L57P 2D AIThe SynGAP1 missense variant L57P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that 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.			0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-10.724	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-1.77	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.90	Benign	0.00	Affected			0.3651	0.1703		-3	-3	-5.4	-16.04
c.178G>T	D60Y 2D AIThe SynGAP1 D60Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the D60Y variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-7.748	In-Between	0.971	Likely Pathogenic	Likely Pathogenic										0.221	Likely Benign	-2.60	Deleterious	0.972	Probably Damaging	0.969	Probably Damaging	3.90	Benign	0.00	Affected			0.0517	0.7790		-4	-3	2.2	48.09
c.187G>C	E63Q 2D AIThe SynGAP1 missense variant E63Q is listed in ClinVar (ID 2132335.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125					Uncertain		1				-4.038	Likely Benign	0.687	Likely Pathogenic	Likely Benign										0.078	Likely Benign	-0.85	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	3.90	Benign	0.00	Affected	4.32	1	0.0970	0.6787		2	2	0.0	-0.98
c.188A>C	E63A 2D AIThe SynGAP1 missense variant E63A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward 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		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.426	Likely Benign	0.850	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.84	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	3.90	Benign	0.00	Affected			0.3281	0.6649		0	-1	5.3	-58.04
c.2060G>T	R687L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign include REVEL, SIFT, ESM1b, and FATHMM, while those that agree on pathogenic are AlphaMissense‑Default, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools—AlphaMissense‑Optimized, FoldX, Foldetta, and premPS—return uncertain or inconclusive results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. Consequently, the evidence does not strongly support either benign or pathogenic classification. The variant is therefore most likely inconclusive, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-6.925	Likely Benign	0.901	Likely Pathogenic	Ambiguous	1.43	Ambiguous	0.3	0.05	Likely Benign	0.74	Ambiguous	0.83	Ambiguous	0.448	Likely Benign	-5.76	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.90	Benign	0.10	Tolerated			0.1252	0.3376		-3	-2	8.3	-43.03
c.2306T>A	L769H 2D AIThe SynGAP1 missense variant L769H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which classify the variant as benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, all of which report the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.038	Likely Benign	0.422	Ambiguous	Likely Benign										0.235	Likely Benign	-1.96	Neutral	0.977	Probably Damaging	0.721	Possibly Damaging	3.90	Benign	0.00	Affected			0.1016	0.0828		-2	-3	-7.0	23.98
c.2306T>C	L769P 2D AIThe SynGAP1 missense variant L769P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.261	Likely Benign	0.338	Likely Benign	Likely Benign										0.200	Likely Benign	-1.75	Neutral	0.925	Possibly Damaging	0.427	Benign	3.90	Benign	0.00	Affected			0.3573	0.1323		-3	-3	-5.4	-16.04
c.2374G>A	E792K 2D AIThe SynGAP1 missense variant E792K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-4.942	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.059	Likely Benign	-2.47	Neutral	0.033	Benign	0.017	Benign	3.90	Benign	0.01	Affected			0.2646	0.7584		0	1	-0.4	-0.94
c.3154G>A	G1052R 2D AISynGAP1 missense variant G1052R is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, and the SGM consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar uncertain status but provides additional support toward a likely benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875					Uncertain		1				-9.050	Likely Pathogenic	0.383	Ambiguous	Likely Benign										0.497	Likely Benign	-0.41	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	3.90	Benign	0.10	Tolerated	3.77	5	0.0976	0.4142		-2	-3	-4.1	99.14
c.3154G>C	G1052R 2D AIThe SynGAP1 missense variant G1052R 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, while polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic outcome; 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, PROVEAN) also yields benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-9.050	Likely Pathogenic	0.383	Ambiguous	Likely Benign										0.497	Likely Benign	-0.41	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	3.90	Benign	0.10	Tolerated	3.77	5	0.0976	0.4142		-2	-3	-4.1	99.14
c.3154G>T	G1052W 2D AIThe SynGAP1 missense variant G1052W is not reported 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 (majority vote) which classifies the variant as 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 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		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-11.322	Likely Pathogenic	0.309	Likely Benign	Likely Benign										0.457	Likely Benign	-0.90	Neutral	0.997	Probably Damaging	0.946	Probably Damaging	3.90	Benign	0.02	Affected			0.0872	0.4046		-7	-2	-0.5	129.16
c.3155G>A	G1052E 2D AIThe SynGAP1 missense variant G1052E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral impact. In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign effect. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-9.869	Likely Pathogenic	0.287	Likely Benign	Likely Benign										0.448	Likely Benign	-0.64	Neutral	0.901	Possibly Damaging	0.537	Possibly Damaging	3.90	Benign	0.12	Tolerated			0.1405	0.3873		0	-2	-3.1	72.06
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.334G>T	G112W 2D AIThe SynGAP1 missense variant G112W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic interpretation. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-6.382	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.98	Deleterious	0.983	Probably Damaging	0.778	Possibly Damaging	3.90	Benign	0.00	Affected			0.0631	0.4212		-7	-2	-0.5	129.16
c.3355G>T	G1119W 2D AIThe SynGAP1 missense variant G1119W is reported in gnomAD (ID 6‑33443907‑G‑T) but has no ClinVar entry. 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, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which is currently absent. 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								6-33443907-G-T			-10.904	Likely Pathogenic	0.336	Likely Benign	Likely Benign										0.386	Likely Benign	-1.19	Neutral	0.997	Probably Damaging	0.949	Probably Damaging	3.90	Benign	0.02	Affected	4.32	2	0.0948	0.4059		-2	-7	-0.5	129.16
c.341A>T	K114M 2D AIThe SynGAP1 missense variant K114M is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points toward a benign effect, and there is no ClinVar entry to contradict this conclusion. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.953	Likely Benign	0.877	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.89	Neutral	0.992	Probably Damaging	0.615	Possibly Damaging	3.90	Benign	0.00	Affected			0.1809	0.4075		0	-1	5.8	3.02
c.377T>A	F126Y 2D AIThe SynGAP1 missense variant F126Y has no ClinVar entry and is not reported in gnomAD. Functional 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, PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-3.519	Likely Benign	0.509	Ambiguous	Likely Benign										0.044	Likely Benign	-1.29	Neutral	0.851	Possibly Damaging	0.221	Benign	3.90	Benign	0.00	Affected			0.1631	0.1907		7	3	-4.1	16.00
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.401G>A	S134N 2D AIThe SynGAP1 missense variant S134N is listed in ClinVar with an “Uncertain” status (ClinVar ID 2819575.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The remaining tools—AlphaMissense‑Optimized and the SGM‑Consensus—are inconclusive; the consensus score is “Likely Benign” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the balance of evidence points to a benign impact, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250					Uncertain		1				-5.534	Likely Benign	0.813	Likely Pathogenic	Ambiguous										0.075	Likely Benign	-1.62	Neutral	0.001	Benign	0.002	Benign	3.90	Benign	0.00	Affected	3.61	5	0.0964	0.4381		1	1	-2.7	27.03
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.451G>A	D151N 2D AIThe SynGAP1 missense variant D151N has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic. The SGM‑Consensus result (Likely Pathogenic) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151N is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-8.479	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.185	Likely Benign	-2.51	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.90	Benign	0.01	Affected			0.1346	0.8186		2	1	0.0	-0.98
c.478C>G	L160V 2D AIThe SynGAP1 missense variant L160V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) indicate that the variant is most likely benign. This conclusion is consistent with the lack of ClinVar evidence and gnomAD presence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-12.506	Likely Pathogenic	0.729	Likely Pathogenic	Likely Benign										0.055	Likely Benign	-1.44	Neutral	0.247	Benign	0.113	Benign	3.90	Benign	0.00	Affected			0.1553	0.3319		2	1	0.4	-14.03
c.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.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.532A>G	K178E 2D AIThe SynGAP1 missense variant K178E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-13.695	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.205	Likely Benign	-2.63	Deleterious	0.905	Possibly Damaging	0.393	Benign	3.90	Benign	0.01	Affected			0.4659	0.0952		0	1	0.4	0.94
c.538T>G	S180A 2D AIThe SynGAP1 missense variant S180A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the S180A variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-10.413	Likely Pathogenic	0.559	Ambiguous	Likely Benign										0.095	Likely Benign	-1.94	Neutral	0.390	Benign	0.079	Benign	3.90	Benign	0.04	Affected			0.5003	0.3788	Weaken	1	1	2.6	-16.00
c.548A>G	H183R 2D AIThe SynGAP1 H183R missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, 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 show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus (majority vote) also pathogenic; Foldetta stability analysis is unavailable. Based on the majority of computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.937	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.368	Likely Benign	-5.43	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.90	Benign	0.13	Tolerated			0.1915	0.2249		2	0	-1.3	19.05
c.563G>T	S188I 2D AIThe SynGAP1 missense variant S188I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus also pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S188I, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-12.133	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.205	Likely Benign	-3.98	Deleterious	0.995	Probably Damaging	0.880	Possibly Damaging	3.90	Benign	0.00	Affected			0.0878	0.6335		-1	-2	5.3	26.08
c.574G>C	A192P 2D AIThe SynGAP1 missense variant A192P is not 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 score (Likely Pathogenic). 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) also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-9.795	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.245	Likely Benign	-3.35	Deleterious	0.999	Probably Damaging	0.946	Probably Damaging	3.90	Benign	0.02	Affected			0.1658	0.3719		1	-1	-3.4	26.04
c.632G>T	S211I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S211I missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM; 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 predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. No evidence from FoldX or Rosetta is available. Overall, the preponderance of evidence indicates 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	PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-17.090	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	1.1	1.05	Ambiguous	1.06	Ambiguous	0.12	Likely Benign	0.251	Likely Benign	-4.94	Deleterious	0.995	Probably Damaging	0.767	Possibly Damaging	3.90	Benign	0.01	Affected			0.0909	0.5220		-1	-2	5.3	26.08
c.77G>A	G26E 2D AIThe SynGAP1 missense variant G26E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375											-3.966	Likely Benign	0.481	Ambiguous	Likely Benign										0.199	Likely Benign	-2.08	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	3.90	Benign	0.00	Affected			0.1623	0.4238		0	-2	-3.1	72.06
c.79C>G	P27A 2D AIThe SynGAP1 missense variant P27A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including high‑accuracy tools, points to a benign effect for P27A, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-3.409	Likely Benign	0.079	Likely Benign	Likely Benign										0.077	Likely Benign	-1.98	Neutral	0.805	Possibly Damaging	0.857	Possibly Damaging	3.90	Benign	0.00	Affected			0.4041	0.5219		1	-1	3.4	-26.04
c.1135T>G	S379A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379A is reported in gnomAD (variant ID 6‑33438040‑T‑G) but has no entry in ClinVar. All available in‑silico predictors classify the change as benign: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625								6-33438040-T-G			-4.300	Likely Benign	0.077	Likely Benign	Likely Benign	-0.22	Likely Benign	0.3	1.03	Ambiguous	0.41	Likely Benign	0.10	Likely Benign	0.217	Likely Benign	-0.50	Neutral	0.012	Benign	0.002	Benign	3.91	Benign	0.21	Tolerated	4.32	11	0.5032	0.5555	Strenghten	1	1	2.6	-16.00
c.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.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.1208A>G	K403R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools—FoldX, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a tie, and Foldetta also predicts benign. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-7.362	In-Between	0.355	Ambiguous	Likely Benign	-0.78	Ambiguous	0.1	0.23	Likely Benign	-0.28	Likely Benign	0.41	Likely Benign	0.335	Likely Benign	-2.56	Deleterious	0.983	Probably Damaging	0.926	Probably Damaging	3.91	Benign	0.15	Tolerated			0.4834	0.1861		3	2	-0.6	28.01
c.1220A>T	Q407L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407L is not 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 agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Four tools are uncertain (AlphaMissense‑Default, FoldX, Rosetta, Foldetta). 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, more tools predict pathogenicity than benign, and the high‑accuracy consensus leans pathogenic. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-12.730	Likely Pathogenic	0.558	Ambiguous	Likely Benign	-0.65	Ambiguous	0.2	-0.69	Ambiguous	-0.67	Ambiguous	0.35	Likely Benign	0.359	Likely Benign	-6.32	Deleterious	0.939	Possibly Damaging	0.838	Possibly Damaging	3.91	Benign	0.02	Affected			0.0585	0.4977		-2	-2	7.3	-14.97
c.145T>A	C49S 2D AIThe SynGAP1 missense variant C49S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic votes). 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 lean toward pathogenicity, but the high‑accuracy tools do not provide definitive support. 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.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.575	Likely Benign	0.704	Likely Pathogenic	Likely Benign										0.260	Likely Benign	-3.07	Deleterious	0.462	Possibly Damaging	0.478	Possibly Damaging	3.91	Benign	0.00	Affected			0.3855	0.1686		0	-1	-3.3	-16.06
c.146G>C	C49S 2D AIThe SynGAP1 missense variant C49S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of conventional tools (five pathogenic vs four benign) lean toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the inconclusive SGM Consensus leave the assessment uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.575	Likely Benign	0.704	Likely Pathogenic	Likely Benign										0.224	Likely Benign	-3.07	Deleterious	0.462	Possibly Damaging	0.478	Possibly Damaging	3.91	Benign	0.00	Affected			0.3855	0.1686		0	-1	-3.3	-16.06
c.148A>C	I50L 2D AIThe SynGAP1 missense variant I50L 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, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is benign; Foldetta results are not available. Overall, the consensus of the available predictions 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		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-3.509	Likely Benign	0.300	Likely Benign	Likely Benign										0.076	Likely Benign	-0.73	Neutral	0.010	Benign	0.004	Benign	3.91	Benign	0.00	Affected			0.0749	0.3247		2	2	-0.7	0.00
c.163C>A	Q55K 2D AIThe SynGAP1 missense variant Q55K is listed in ClinVar (ID 520688.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33423572‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000					Uncertain		2	6-33423572-C-A	24	1.49e-5	-5.840	Likely Benign	0.612	Likely Pathogenic	Likely Benign										0.085	Likely Benign	-1.21	Neutral	0.140	Benign	0.184	Benign	3.91	Benign	0.00	Affected	4.32	1	0.2047	0.4129		1	1	-0.4	0.04
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.178G>C	D60H 2D AIThe SynGAP1 missense variant D60H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the 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		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-5.257	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-1.59	Neutral	0.972	Probably Damaging	0.969	Probably Damaging	3.91	Benign	0.00	Affected			0.1433	0.8401		1	-1	0.3	22.05
c.179A>T	D60V 2D AIThe SynGAP1 D60V missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that 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, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (7 of 10) indicate pathogenicity, while only three suggest benignity. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-6.576	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.254	Likely Benign	-2.72	Deleterious	0.972	Probably Damaging	0.954	Probably Damaging	3.91	Benign	0.00	Affected			0.0765	0.7962		-2	-3	7.7	-15.96
c.2060G>A	R687Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687Q is annotated in ClinVar as benign (ClinVar ID 2693600.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, SGM‑Consensus indicating pathogenicity, and Foldetta (integrating FoldX‑MD and Rosetta outputs) classifying it as benign. With three high‑accuracy tools giving benign or uncertain results and only one (SGM‑Consensus) suggesting pathogenicity, the overall evidence leans toward a benign effect. This prediction aligns with the ClinVar benign classification, indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000					Likely Benign		1				-10.002	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.92	Ambiguous	0.1	-0.37	Likely Benign	0.28	Likely Benign	1.55	Destabilizing	0.401	Likely Benign	-3.37	Deleterious	1.000	Probably Damaging	0.844	Possibly Damaging	3.91	Benign	0.03	Affected	3.42	17	0.2143	0.1952		1	1	1.0	-28.06
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.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.2912C>G	P971R 2D AIThe SynGAP1 missense variant P971R is not reported 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	0.951523	Binding	0.545	0.905	0.625											-4.407	Likely Benign	0.149	Likely Benign	Likely Benign										0.042	Likely Benign	-1.01	Neutral	0.453	Possibly Damaging	0.078	Benign	3.91	Benign	0.00	Affected			0.1306	0.3818		0	-2	-2.9	59.07
c.3236G>C	S1079T 2D AIThe SynGAP1 missense variant S1079T is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. 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. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly suggests the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for S1079T. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-3.225	Likely Benign	0.163	Likely Benign	Likely Benign										0.023	Likely Benign	-1.28	Neutral	0.001	Benign	0.003	Benign	3.91	Benign	0.00	Affected			0.1283	0.5920		1	1	0.1	14.03
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.379C>G	R127G 2D AIThe SynGAP1 R127G 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. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN; it yields a “Likely Benign” classification (3 benign vs. 1 pathogenic). AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625											-1.062	Likely Benign	0.700	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-2.17	Neutral	0.287	Benign	0.038	Benign	3.91	Benign	0.01	Affected			0.3561	0.3037		-3	-2	4.1	-99.14
c.3947A>T	N1316I 2D AIThe SynGAP1 missense variant N1316I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). 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 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.			0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750											-4.829	Likely Benign	0.635	Likely Pathogenic	Likely Benign										0.147	Likely Benign	-2.86	Deleterious	0.009	Benign	0.004	Benign	3.91	Benign	0.00	Affected			0.0719	0.5354		-2	-3	8.0	-0.94
c.3989A>C	Q1330P 2D AIThe SynGAP1 missense variant Q1330P is listed in gnomAD (ID 6‑33451863‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM; pathogenic predictions come from 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 are mixed: AlphaMissense‑Optimized yields an “Uncertain” result, SGM‑Consensus confirms a benign leaning, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence favors a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875								6-33451863-A-C			-3.087	Likely Benign	0.814	Likely Pathogenic	Ambiguous										0.076	Likely Benign	-2.45	Neutral	0.898	Possibly Damaging	0.441	Benign	3.91	Benign	0.03	Affected	3.77	5	0.2266	0.4983		-1	0	1.9	-31.01
c.3990G>C	Q1330H 2D AIThe SynGAP1 missense variant Q1330H is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two consensus 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, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM‑Consensus also reports it as likely benign, and Foldetta (which integrates FoldX‑MD and Rosetta stability calculations) has no available result for this residue. Based on the preponderance of benign predictions from multiple independent algorithms and the lack of pathogenic evidence, the variant is most likely benign. 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		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875											-3.557	Likely Benign	0.477	Ambiguous	Likely Benign										0.066	Likely Benign	-1.91	Neutral	0.969	Probably Damaging	0.732	Possibly Damaging	3.91	Benign	0.02	Affected			0.1190	0.3996		3	0	0.3	9.01
c.3990G>T	Q1330H 2D AIThe SynGAP1 missense variant Q1330H is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two consensus 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, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM‑Consensus also reports it as likely benign, and Foldetta (which integrates FoldX‑MD and Rosetta stability calculations) has no available result for this residue. Based on the preponderance of benign predictions from multiple independent algorithms and the lack of pathogenic evidence, the variant is most likely benign. 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		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875											-3.557	Likely Benign	0.477	Ambiguous	Likely Benign										0.066	Likely Benign	-1.91	Neutral	0.969	Probably Damaging	0.732	Possibly Damaging	3.91	Benign	0.02	Affected			0.1190	0.3996		3	0	0.3	9.01
c.440A>G	Q147R 2D AIThe SynGAP1 missense variant Q147R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑to‑2 split, and Foldetta results are unavailable. Overall, more tools predict a benign outcome (five vs. three pathogenic predictions, with one uncertain). Therefore, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-12.301	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.166	Likely Benign	-2.22	Neutral	0.079	Benign	0.052	Benign	3.91	Benign	0.02	Affected			0.1760	0.1042		1	1	-1.0	28.06
c.452A>C	D151A 2D AIThe SynGAP1 D151A missense variant is listed in gnomAD (ID 6‑33432749‑A‑C) but has no ClinVar entry. Functional prediction tools fall into two groups: benign predictions come from REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic 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 Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625								6-33432749-A-C	1	6.21e-7	-9.693	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.326	Likely Benign	-4.51	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.91	Benign	0.01	Affected	3.61	5	0.4286	0.7424		-2	0	5.3	-44.01
c.509G>A	R170Q 2D AISynGAP1 missense variant R170Q is listed in ClinVar as Pathogenic and is not reported in gnomAD. Computational predictors show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive; Foldetta stability analysis is unavailable. Thus, no single method or high‑accuracy consensus strongly supports pathogenicity. The variant is most likely benign according to the current computational evidence, which contradicts the ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250					Pathogenic/Likely path.		6				-9.021	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous										0.221	Likely Benign	-2.31	Neutral	0.947	Possibly Damaging	0.342	Benign	3.91	Benign	0.00	Affected	3.74	4	0.2524	0.2299		1	1	1.0	-28.06																10.1016/j.ajhg.2020.11.011
c.562A>G	S188G 2D AIThe SynGAP1 missense variant S188G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is “Likely Pathogenic.” AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.113	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-3.10	Deleterious	0.882	Possibly Damaging	0.404	Benign	3.91	Benign	0.00	Affected			0.3045	0.5542		1	0	0.4	-30.03
c.575C>G	A192G 2D AIThe SynGAP1 missense variant A192G is not 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, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-9.003	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous										0.133	Likely Benign	-3.00	Deleterious	0.989	Probably Damaging	0.621	Possibly Damaging	3.91	Benign	0.02	Affected			0.2081	0.2857		1	0	-2.2	-14.03
c.79C>T	P27S 2D AIThe SynGAP1 missense variant P27S is reported in gnomAD (ID 6‑33423488‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (derived from the majority of these high‑accuracy predictors) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that P27S is most likely benign, and this assessment does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375								6-33423488-C-T	1	6.20e-7	-2.891	Likely Benign	0.098	Likely Benign	Likely Benign										0.063	Likely Benign	-2.01	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	3.91	Benign	0.00	Affected	4.32	1	0.3916	0.5443		-1	1	0.8	-10.04
c.197C>G	P66R 2D AIThe SynGAP1 missense variant P66R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the majority of evidence points toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-2.708	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.221	Likely Benign	-2.23	Neutral	0.972	Probably Damaging	0.804	Possibly Damaging	3.92	Benign	0.00	Affected			0.1636	0.3928		0	-2	-2.9	59.07
c.197C>T	P66L 2D AIThe SynGAP1 missense variant P66L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized calling the variant pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are not available. Overall, the predictions are split evenly between benign and pathogenic, with high‑accuracy tools providing opposing conclusions. Consequently, the variant’s impact remains uncertain and does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-2.437	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.48	Neutral	0.909	Possibly Damaging	0.713	Possibly Damaging	3.92	Benign	0.00	Affected			0.2412	0.6687		-3	-3	5.4	16.04
c.2375A>C	E792A 2D AIThe SynGAP1 missense variant E792A is catalogued in gnomAD (ID 6‑33442927‑A‑C) but has no ClinVar submission. Functional prediction tools cluster into two groups: benign (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, SIFT). The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors benign. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875								6-33442927-A-C	1	6.20e-7	-3.248	Likely Benign	0.515	Ambiguous	Likely Benign										0.060	Likely Benign	-3.35	Deleterious	0.000	Benign	0.001	Benign	3.92	Benign	0.01	Affected	3.64	6	0.4586	0.7544		-1	0	5.3	-58.04
c.238A>G	K80E 2D AIThe SynGAP1 K80E missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Overall, the balance of evidence favors a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K80E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.605	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.034	Likely Benign	-0.91	Neutral	0.225	Benign	0.027	Benign	3.92	Benign	0.00	Affected			0.3850	0.0952		0	1	0.4	0.94
c.242T>C	L81P 2D AIThe SynGAP1 missense variant L81P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of 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		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-4.413	Likely Benign	0.827	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-1.51	Neutral	0.919	Possibly Damaging	0.226	Benign	3.92	Benign	0.00	Affected			0.3062	0.1818		-3	-3	-5.4	-16.04
c.271G>A	E91K 2D AISynGAP1 E91K is not reported in ClinVar and is absent from gnomAD. Computational predictors fall into two groups: benign calls (REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus “Likely Benign”) and pathogenic calls (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy tools give conflicting results: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts benign; Foldetta data are unavailable. Consequently, the evidence is split, but the consensus of the most reliable predictors leans toward a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-4.964	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-1.07	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.92	Benign	0.00	Affected			0.2693	0.7444		0	1	-0.4	-0.94
c.2944T>C	Y982H 2D AIThe SynGAP1 missense variant Y982H has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 evidence is mixed, but the majority of consensus‑based and high‑accuracy tools lean toward a benign interpretation. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-2.675	Likely Benign	0.893	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-0.63	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	3.92	Benign	0.00	Affected			0.2352	0.0545		0	2	-1.9	-26.03
c.31G>A	G11R 2D AIThe SynGAP1 missense variant G11R is catalogued in gnomAD (ID 6‑33420295‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from 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; the Foldetta protein‑folding 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 reported). 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								6-33420295-G-A			-3.418	Likely Benign	0.428	Ambiguous	Likely Benign										0.102	Likely Benign	-0.47	Neutral	0.498	Possibly Damaging	0.026	Benign	3.92	Benign	0.00	Affected	4.32	1	0.1022	0.4596		-2	-3	-4.1	99.14
c.31G>C	G11R 2D AIThe SynGAP1 missense variant G11R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.501027	Binding	0.348	0.915	0.375											-3.418	Likely Benign	0.428	Ambiguous	Likely Benign										0.109	Likely Benign	-0.47	Neutral	0.498	Possibly Damaging	0.026	Benign	3.92	Benign	0.00	Affected	4.32	1	0.1022	0.4596		-2	-3	-4.1	99.14
c.3215A>C	K1072T 2D AIThe SynGAP1 missense variant K1072T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus result is benign; Foldetta predictions are unavailable. Overall, the balance of evidence leans toward a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.557	Likely Benign	0.834	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-1.31	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.06	Tolerated			0.1967	0.4307		0	-1	3.2	-27.07
c.3216G>C	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3216G>T	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.380G>C	R127P 2D AIThe SynGAP1 missense variant R127P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. In contrast, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default predict pathogenicity. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors a benign outcome. No Foldetta stability assessment is available, so it does not influence the interpretation. Overall, the preponderance of evidence points to a benign effect for R127P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625											-0.375	Likely Benign	0.703	Likely Pathogenic	Likely Benign										0.187	Likely Benign	-2.25	Neutral	0.748	Possibly Damaging	0.110	Benign	3.92	Benign	0.01	Affected			0.2295	0.3741		0	-2	2.9	-59.07
c.380G>T	R127L 2D AIThe SynGAP1 missense variant R127L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from 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 results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625											-0.626	Likely Benign	0.643	Likely Pathogenic	Likely Benign										0.127	Likely Benign	-2.02	Neutral	0.080	Benign	0.012	Benign	3.92	Benign	0.01	Affected			0.1965	0.3834		-3	-2	8.3	-43.03
c.391G>C	G131R 2D AIThe SynGAP1 missense variant G131R is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑to‑2 split and therefore does not contribute evidence. 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 tools predict a pathogenic effect, and the variant is most likely pathogenic based on current predictions, which does not contradict the ClinVar “Uncertain” status. 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					Uncertain		1				-6.564	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.82	Deleterious	0.983	Probably Damaging	0.656	Possibly Damaging	3.92	Benign	0.00	Affected	3.61	5	0.1070	0.4667		-2	-3	-4.1	99.14
c.392G>A	G131D 2D AIThe SynGAP1 missense variant G131D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools (ESM1b and AlphaMissense‑Optimized) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence (four pathogenic, three benign, two uncertain) leans toward pathogenicity. This prediction does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-7.477	In-Between	0.950	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-3.29	Deleterious	0.888	Possibly Damaging	0.435	Benign	3.92	Benign	0.02	Affected			0.2093	0.2550		1	-1	-3.1	58.04
c.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.3967C>G	P1323A 2D AIThe SynGAP1 missense variant P1323A is catalogued in gnomAD (ID 6‑33451841‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, 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, also indicates a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign; Foldetta results are not available. Overall, the consensus of available predictions points to a benign impact for P1323A, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875								6-33451841-C-G			-4.802	Likely Benign	0.053	Likely Benign	Likely Benign										0.040	Likely Benign	-0.73	Neutral	0.011	Benign	0.017	Benign	3.92	Benign	0.00	Affected	4.32	1	0.3743	0.3976		-1	1	3.4	-26.04
c.3989A>T	Q1330L 2D AIThe SynGAP1 missense variant Q1330L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875											-3.780	Likely Benign	0.417	Ambiguous	Likely Benign										0.110	Likely Benign	-2.74	Deleterious	0.784	Possibly Damaging	0.341	Benign	3.92	Benign	0.02	Affected			0.0741	0.5480		-2	-2	7.3	-14.97
c.440A>T	Q147L 2D AIThe SynGAP1 missense variant Q147L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic interpretation, and this is not contradicted by any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.879	Likely Pathogenic	0.740	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-3.51	Deleterious	0.079	Benign	0.037	Benign	3.92	Benign	0.03	Affected			0.0861	0.4927		-2	-2	7.3	-14.97
c.443C>G	P148R 2D AIThe SynGAP1 missense variant P148R is not 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 score (Likely Pathogenic). 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) also indicates 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 suggests that P148R 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		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-12.079	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.174	Likely Benign	-3.17	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.92	Benign	0.01	Affected			0.1615	0.3100		0	-2	-2.9	59.07
c.467T>G	F156C 2D AIThe SynGAP1 missense variant F156C is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as “Likely Pathogenic.” No Foldetta stability analysis is available for this variant. Overall, the majority of predictions, including the high‑accuracy tools, indicate that F156C is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.521964	Binding	0.284	0.785	0.500					Uncertain		1				-13.658	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.297	Likely Benign	-3.54	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.92	Benign	0.00	Affected			0.3030	0.1291		-4	-2	-0.3	-44.04
c.481C>A	P161T 2D AIThe SynGAP1 missense variant P161T has no ClinVar entry and is not reported in gnomAD. Computational predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-8.759	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.153	Likely Benign	-3.77	Deleterious	0.535	Possibly Damaging	0.310	Benign	3.92	Benign	0.00	Affected			0.1891	0.5038		0	-1	0.9	3.99
c.482C>T	P161L 2D AIThe SynGAP1 missense variant P161L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized also predicts Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of predictions (seven pathogenic vs. four benign) indicate that P161L 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		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-12.159	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic										0.236	Likely Benign	-4.48	Deleterious	0.001	Benign	0.003	Benign	3.92	Benign	0.00	Affected			0.2424	0.5902		-3	-3	5.4	16.04
c.500A>T	D167V 2D AIThe SynGAP1 D167V variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-14.388	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic										0.396	Likely Benign	-4.03	Deleterious	0.535	Possibly Damaging	0.247	Benign	3.92	Benign	0.00	Affected			0.0709	0.6905		-2	-3	7.7	-15.96
c.518T>C	L173P 2D AIThe SynGAP1 missense variant L173P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split; Foldetta results are not available. Consequently, the computational evidence is evenly divided, providing no clear advantage for either benign or pathogenic classification. The variant is therefore most likely inconclusive 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.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-8.758	Likely Pathogenic	0.918	Likely Pathogenic	Ambiguous										0.135	Likely Benign	-2.38	Neutral	0.838	Possibly Damaging	0.466	Possibly Damaging	3.92	Benign	0.15	Tolerated			0.3318	0.1382		-3	-3	-5.4	-16.04
c.562A>C	S188R 2D AIThe SynGAP1 missense variant S188R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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, 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 S188R 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.269	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.563G>A	S188N 2D AIThe SynGAP1 missense variant S188N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of available predictions (five benign vs three pathogenic) suggest a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.307	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-2.34	Neutral	0.259	Benign	0.048	Benign	3.92	Benign	0.01	Affected			0.1420	0.5658		1	1	-2.7	27.03
c.563G>C	S188T 2D AIThe SynGAP1 missense variant S188T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign (two benign versus one pathogenic vote). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion does not contradict any ClinVar annotation, as none exists for S188T. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-7.906	In-Between	0.801	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-1.97	Neutral	0.948	Possibly Damaging	0.484	Possibly Damaging	3.92	Benign	0.13	Tolerated			0.1491	0.7492		1	1	0.1	14.03
c.564T>A	S188R 2D AIThe SynGAP1 missense variant S188R 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, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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, a protein‑folding stability method, did not provide a result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S188R 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.564T>G	S188R 2D AIThe SynGAP1 missense variant S188R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: 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, a protein‑folding stability method, did not provide a 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.263	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.631A>G	S211G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, and ESM1b; Rosetta is uncertain. High‑accuracy methods give a benign result for AlphaMissense‑Optimized and for Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic). No evidence from ClinVar contradicts these predictions. Overall, the balance of evidence—including the unanimous benign calls from the high‑accuracy tools—suggests that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.895	Likely Pathogenic	0.265	Likely Benign	Likely Benign	0.30	Likely Benign	0.2	0.54	Ambiguous	0.42	Likely Benign	1.07	Destabilizing	0.067	Likely Benign	-3.17	Deleterious	0.787	Possibly Damaging	0.404	Benign	3.92	Benign	0.07	Tolerated			0.2560	0.4337		1	0	0.4	-30.03
c.73C>T	R25W 2D AIThe SynGAP1 missense variant R25W is listed in ClinVar with an “Uncertain” status (ClinVar ID 2993054.0) and is present in gnomAD (ID 6‑33423482‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign 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 Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375					Uncertain		2	6-33423482-C-T	6	3.72e-6	-5.133	Likely Benign	0.549	Ambiguous	Likely Benign										0.158	Likely Benign	-1.60	Neutral	0.994	Probably Damaging	0.919	Probably Damaging	3.92	Benign	0.00	Affected	4.32	1	0.1224	0.3938		-3	2	3.6	30.03
c.88C>A	H30N 2D AIThe SynGAP1 missense variant H30N is not reported in ClinVar and is absent from gnomAD. Consensus among most in silico predictors is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect, while only SIFT predicts pathogenicity. Grouping the tools, the benign‑predicting set (nine tools) overwhelmingly outweighs the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-3.096	Likely Benign	0.108	Likely Benign	Likely Benign										0.052	Likely Benign	-1.91	Neutral	0.273	Benign	0.380	Benign	3.92	Benign	0.00	Affected			0.2699	0.3818		2	1	-0.3	-23.04
c.1118G>C	G373A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G373A is not reported in ClinVar and is absent from gnomAD. Functional prediction consensus shows a predominance of benign calls: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict a benign effect. Pathogenic predictions are limited to SIFT and FoldX, while Rosetta and Foldetta yield uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta remains inconclusive. Overall, the majority of evidence indicates that G373A is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625											-5.181	Likely Benign	0.099	Likely Benign	Likely Benign	2.44	Destabilizing	0.8	0.69	Ambiguous	1.57	Ambiguous	-0.01	Likely Benign	0.227	Likely Benign	-0.47	Neutral	0.000	Benign	0.000	Benign	3.93	Benign	0.01	Affected			0.4172	0.5053		1	0	2.2	14.03
c.1157G>A	G386E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G386E is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438062‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are FoldX, Foldetta, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Overall, the majority of tools predict a pathogenic impact, suggesting the variant is most likely pathogenic, which does not contradict the ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750					Uncertain		1	6-33438062-G-A			-9.286	Likely Pathogenic	0.686	Likely Pathogenic	Likely Benign	3.69	Destabilizing	2.9	0.79	Ambiguous	2.24	Destabilizing	0.54	Ambiguous	0.447	Likely Benign	-0.83	Neutral	0.860	Possibly Damaging	0.354	Benign	3.93	Benign	0.01	Affected	4.32	3	0.1543	0.3354		-2	0	-3.1	72.06
c.1157G>C	G386A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change G386A has no ClinVar entry and is not reported in gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (SGM‑Consensus, REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar) and pathogenic (FoldX, polyPhen‑2 HumDiv, SIFT). Two tools report uncertainty: Rosetta and Foldetta. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a benign effect for G386A. 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	C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750											-6.453	Likely Benign	0.112	Likely Benign	Likely Benign	2.14	Destabilizing	0.7	1.05	Ambiguous	1.60	Ambiguous	0.14	Likely Benign	0.331	Likely Benign	-0.55	Neutral	0.718	Possibly Damaging	0.332	Benign	3.93	Benign	0.05	Affected			0.3815	0.4868		1	0	2.2	14.03
c.1186G>A	G396S 2D AIThe SynGAP1 missense variant G396S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No tool predicts pathogenicity. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500											-3.934	Likely Benign	0.088	Likely Benign	Likely Benign	1.76	Ambiguous	1.6	1.12	Ambiguous	1.44	Ambiguous	0.10	Likely Benign	0.223	Likely Benign	-0.99	Neutral	0.004	Benign	0.003	Benign	3.93	Benign	0.56	Tolerated			0.2668	0.4894		1	0	-0.4	30.03
c.1187G>C	G396A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G396A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign verdict, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Consequently, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500											-3.655	Likely Benign	0.103	Likely Benign	Likely Benign	1.74	Ambiguous	0.7	1.90	Ambiguous	1.82	Ambiguous	0.41	Likely Benign	0.274	Likely Benign	-1.28	Neutral	0.062	Benign	0.024	Benign	3.93	Benign	0.84	Tolerated			0.3846	0.5255		1	0	2.2	14.03
c.1390T>C	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.435	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>A	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>G	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.143T>G	F48C 2D AIThe SynGAP1 missense variant F48C 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, 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 the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (3 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-5.950	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.153	Likely Benign	-2.31	Neutral	0.953	Possibly Damaging	0.431	Benign	3.93	Benign	0.00	Affected			0.2657	0.1962		-4	-2	-0.3	-44.04
c.238A>C	K80Q 2D AIThe SynGAP1 missense variant K80Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-4.475	Likely Benign	0.662	Likely Pathogenic	Likely Benign										0.064	Likely Benign	-0.81	Neutral	0.414	Benign	0.040	Benign	3.93	Benign	0.00	Affected			0.4373	0.1132		1	1	0.4	-0.04
c.242T>A	L81Q 2D AIThe SynGAP1 missense variant L81Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-5.055	Likely Benign	0.517	Ambiguous	Likely Benign										0.052	Likely Benign	-1.22	Neutral	0.919	Possibly Damaging	0.226	Benign	3.93	Benign	0.00	Affected			0.1046	0.0888		-2	-2	-7.3	14.97
c.2581T>C	S861P 2D AIThe SynGAP1 missense variant S861P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for S861P, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-4.256	Likely Benign	0.107	Likely Benign	Likely Benign										0.116	Likely Benign	-1.65	Neutral	0.960	Probably Damaging	0.761	Possibly Damaging	3.93	Benign	0.13	Tolerated			0.1830	0.6011		1	-1	-0.8	10.04
c.2582C>T	S861L 2D AIThe SynGAP1 missense variant S861L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443134‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. No Foldetta stability prediction is available for this variant. Overall, the computational evidence overwhelmingly points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250					Uncertain		1	6-33443134-C-T	2	1.24e-6	-4.966	Likely Benign	0.219	Likely Benign	Likely Benign										0.144	Likely Benign	-2.10	Neutral	0.904	Possibly Damaging	0.355	Benign	3.93	Benign	0.07	Tolerated	4.32	3	0.1186	0.5927		-3	-2	4.6	26.08
c.2912C>T	P971L 2D AIThe SynGAP1 missense variant P971L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625											-4.892	Likely Benign	0.070	Likely Benign	Likely Benign										0.030	Likely Benign	-1.57	Neutral	0.144	Benign	0.026	Benign	3.93	Benign	0.00	Affected			0.2046	0.5985		-3	-3	5.4	16.04
c.3155G>C	G1052A 2D AIThe SynGAP1 missense variant G1052A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-6.945	Likely Benign	0.086	Likely Benign	Likely Benign										0.382	Likely Benign	-0.14	Neutral	0.649	Possibly Damaging	0.287	Benign	3.93	Benign	1.00	Tolerated			0.3259	0.4949		1	0	2.2	14.03
c.3236G>A	S1079N 2D AIThe SynGAP1 missense variant S1079N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-4.989	Likely Benign	0.505	Ambiguous	Likely Benign										0.026	Likely Benign	-0.97	Neutral	0.001	Benign	0.001	Benign	3.93	Benign	0.00	Affected			0.1225	0.4657		1	1	-2.7	27.03
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.3356G>A	G1119E 2D AIThe SynGAP1 missense variant G1119E is reported in gnomAD (variant ID 6-33443908‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “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 G1119E 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		0.827927	Disordered	0.818538	Binding	0.339	0.928	0.875								6-33443908-G-A	1	6.61e-7	-9.151	Likely Pathogenic	0.338	Likely Benign	Likely Benign										0.284	Likely Benign	-0.41	Neutral	0.005	Benign	0.013	Benign	3.93	Benign	0.12	Tolerated	4.32	2	0.1654	0.4259		-2	0	-3.1	72.06
c.3356G>C	G1119A 2D AIThe SynGAP1 missense variant G1119A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.818538	Binding	0.339	0.928	0.875											-6.703	Likely Benign	0.082	Likely Benign	Likely Benign										0.201	Likely Benign	-0.33	Neutral	0.393	Benign	0.187	Benign	3.93	Benign	1.00	Tolerated			0.3591	0.4957		1	0	2.2	14.03
c.443C>T	P148L 2D AIThe SynGAP1 missense variant P148L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the consensus of the majority of tools points to a pathogenic effect. Because there is no ClinVar classification to contradict this, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-10.375	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-3.29	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.93	Benign	0.01	Affected			0.2229	0.5714		-3	-3	5.4	16.04
c.482C>G	P161R 2D AIThe SynGAP1 missense variant P161R is not 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		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-13.014	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.302	Likely Benign	-4.16	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.93	Benign	0.00	Affected			0.1716	0.2900		0	-2	-2.9	59.07
c.499G>C	D167H 2D AIThe SynGAP1 missense variant D167H is not 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		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-12.606	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic										0.338	Likely Benign	-3.29	Deleterious	0.898	Possibly Damaging	0.557	Possibly Damaging	3.93	Benign	0.00	Affected			0.1478	0.7563		1	-1	0.3	22.05
c.500A>G	D167G 2D AIThe SynGAP1 missense variant D167G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of 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 not available for this variant. Overall, the majority of evidence points to a pathogenic impact. The prediction is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-11.806	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous										0.338	Likely Benign	-3.20	Deleterious	0.141	Benign	0.091	Benign	3.93	Benign	0.00	Affected			0.3580	0.6750		1	-1	3.1	-58.04
c.575C>A	A192E 2D AIThe SynGAP1 missense variant A192E is not 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 has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-12.188	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.268	Likely Benign	-3.52	Deleterious	0.997	Probably Damaging	0.888	Possibly Damaging	3.93	Benign	0.01	Affected			0.0939	0.1628		0	-1	-5.3	58.04
c.88C>G	H30D 2D AIThe SynGAP1 missense variant H30D is not reported 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 H30D, 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		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-2.838	Likely Benign	0.318	Likely Benign	Likely Benign										0.150	Likely Benign	-2.25	Neutral	0.462	Possibly Damaging	0.599	Possibly Damaging	3.93	Benign	0.00	Affected			0.3048	0.3296		1	-1	-0.3	-22.05
c.907G>T	G303W 2D 3DClick to see structure in 3D Viewer AIClinVar reports no entry for this SynGAP1 G303W variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta’s stability prediction is also unavailable. Overall, the evidence is evenly split between benign and pathogenic predictions, providing no clear bias toward either outcome. This balanced prediction does not contradict ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.450668	Structured	0.271087	Uncertain	0.630	0.254	0.250											-9.041	Likely Pathogenic	0.579	Likely Pathogenic	Likely Benign	1.69	Ambiguous	0.3	1.11	Ambiguous	1.40	Ambiguous	0.28	Likely Benign	0.157	Likely Benign	-1.63	Neutral	0.983	Probably Damaging	0.813	Possibly Damaging	3.93	Benign	0.00	Affected			0.0663	0.4553		-7	-2	-0.5	129.16
c.90C>A	H30Q 2D AIThe SynGAP1 H30Q missense change is catalogued in gnomAD (ID 6‑33423499‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: six methods (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all indicate a benign effect, while three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT) predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (derived from the four benign‑predicting tools) also yields a benign verdict. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with ClinVar, which currently contains no classification for H30Q. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250								6-33423499-C-A	1	6.20e-7	-3.016	Likely Benign	0.142	Likely Benign	Likely Benign										0.068	Likely Benign	-2.21	Neutral	0.462	Possibly Damaging	0.599	Possibly Damaging	3.93	Benign	0.00	Affected	4.32	1	0.2409	0.4422		0	3	-0.3	-9.01
c.90C>G	H30Q 2D AIThe SynGAP1 missense variant H30Q 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. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, 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 assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-3.016	Likely Benign	0.142	Likely Benign	Likely Benign										0.068	Likely Benign	-2.21	Neutral	0.462	Possibly Damaging	0.599	Possibly Damaging	3.93	Benign	0.00	Affected	4.32	1	0.2409	0.4422		0	3	-0.3	-9.01
c.179A>G	D60G 2D AIThe SynGAP1 D60G 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, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict 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		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-4.423	Likely Benign	0.775	Likely Pathogenic	Likely Benign										0.128	Likely Benign	-1.67	Neutral	0.805	Possibly Damaging	0.857	Possibly Damaging	3.94	Benign	0.00	Affected			0.4143	0.7069		1	-1	3.1	-58.04
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.2330T>C	L777P 2D AIThe SynGAP1 missense variant L777P is catalogued in gnomAD (6‑33442488‑T‑C) 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 reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for the variant, 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		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250								6-33442488-T-C			-5.807	Likely Benign	0.361	Ambiguous	Likely Benign										0.255	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.94	Benign	0.00	Affected	3.64	6	0.3732	0.1664		-3	-3	-5.4	-16.04
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.256G>A	V86I 2D AIThe SynGAP1 missense variant V86I is listed in ClinVar (ID 588267.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the variant as benign or likely benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the majority of predictions indicate that V86I is most likely benign, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500					Uncertain		1				-4.726	Likely Benign	0.338	Likely Benign	Likely Benign										0.076	Likely Benign	-0.31	Neutral	0.267	Benign	0.097	Benign	3.94	Benign	0.00	Affected	4.32	1	0.0887	0.4417		4	3	0.3	14.03
c.2575A>T	S859C 2D AIThe SynGAP1 missense variant S859C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN reports the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.268	Likely Pathogenic	0.136	Likely Benign	Likely Benign										0.195	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.94	Benign	0.03	Affected			0.1046	0.6153		0	-1	3.3	16.06
c.2668C>T	R890C 2D AIThe SynGAP1 missense variant R890C is listed in ClinVar as benign and is present in gnomAD (6-33443220-C‑T). Functional prediction tools show mixed results: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus also indicates benign; Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect, which is consistent with the ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625					Benign		1	6-33443220-C-T	9	5.58e-6	-5.786	Likely Benign	0.402	Ambiguous	Likely Benign										0.200	Likely Benign	-3.38	Deleterious	1.000	Probably Damaging	0.971	Probably Damaging	3.94	Benign	0.04	Affected	4.32	4	0.3626	0.2206		-4	-3	7.0	-53.05
c.2929G>C	A977P 2D AIThe SynGAP1 missense variant A977P is not reported 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 A977P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.975330	Binding	0.306	0.884	0.625											-2.665	Likely Benign	0.135	Likely Benign	Likely Benign										0.094	Likely Benign	-1.12	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	3.94	Benign	0.02	Affected			0.2405	0.5212		1	-1	-3.4	26.04
c.3233T>C	V1078A 2D AIThe SynGAP1 missense variant V1078A is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only two tools predict pathogenicity: SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of predictions indicate that V1078A is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750											-2.794	Likely Benign	0.690	Likely Pathogenic	Likely Benign										0.089	Likely Benign	-0.27	Neutral	0.011	Benign	0.006	Benign	3.94	Benign	0.02	Affected			0.2679	0.2546		0	0	-2.4	-28.05
c.334G>A	G112R 2D AIThe SynGAP1 missense variant G112R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; 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 standard predictors lean toward a benign impact, and this is not contradicted by any ClinVar annotation. 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.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-3.680	Likely Benign	0.866	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-3.31	Deleterious	0.002	Benign	0.004	Benign	3.94	Benign	0.00	Affected			0.0983	0.3978		-3	-2	-4.1	99.14
c.334G>C	G112R 2D AIThe SynGAP1 missense variant G112R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; 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 standard predictors lean toward a benign impact, and this is not contradicted by any ClinVar annotation. 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.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-3.680	Likely Benign	0.866	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-3.31	Deleterious	0.002	Benign	0.004	Benign	3.94	Benign	0.00	Affected			0.0983	0.3978		-3	-2	-4.1	99.14
c.439C>A	Q147K 2D AIThe SynGAP1 missense variant Q147K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of available predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-12.562	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.084	Likely Benign	-2.12	Neutral	0.018	Benign	0.025	Benign	3.94	Benign	0.03	Affected			0.2012	0.3351		1	1	-0.4	0.04
c.439C>G	Q147E 2D AIThe SynGAP1 missense variant Q147E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy AlphaMissense‑Optimized result is unavailable, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (2 pathogenic, 2 benign) and is therefore considered uncertain. Foldetta, which would assess protein‑folding stability, has no reported output for this variant, so its result is unavailable. Overall, the majority of evidence (five benign vs. three pathogenic) points to a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-10.347	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-1.47	Neutral	0.018	Benign	0.025	Benign	3.94	Benign	0.02	Affected			0.1561	0.1838		2	2	0.0	0.98
c.481C>T	P161S 2D AIThe SynGAP1 missense variant P161S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-8.550	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.085	Likely Benign	-3.63	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.94	Benign	0.00	Affected			0.3628	0.4597		1	-1	0.8	-10.04
c.493A>T	S165C 2D AIThe SynGAP1 missense variant S165C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for S165C, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-8.425	Likely Pathogenic	0.367	Ambiguous	Likely Benign										0.304	Likely Benign	-1.92	Neutral	0.938	Possibly Damaging	0.498	Possibly Damaging	3.94	Benign	0.00	Affected			0.1306	0.5534		0	-1	3.3	16.06
c.518T>A	L173Q 2D AIThe SynGAP1 missense variant L173Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. 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 and the SGM‑Consensus indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-5.605	Likely Benign	0.850	Likely Pathogenic	Ambiguous										0.133	Likely Benign	-1.72	Neutral	0.022	Benign	0.022	Benign	3.94	Benign	0.08	Tolerated			0.1028	0.0919		-2	-2	-7.3	14.97
c.536A>T	E179V 2D AIThe SynGAP1 missense variant E179V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-10.930	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-4.34	Deleterious	0.596	Possibly Damaging	0.328	Benign	3.94	Benign	0.01	Affected			0.1077	0.7864		-2	-2	7.7	-29.98
c.581A>T	E194V 2D AIThe SynGAP1 missense variant E194V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, 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 a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-10.261	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.284	Likely Benign	-4.67	Deleterious	0.580	Possibly Damaging	0.254	Benign	3.94	Benign	0.00	Affected			0.0623	0.5469		-2	-2	7.7	-29.98
c.620A>T	K207M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact; premPS is uncertain. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.596	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	-0.22	Likely Benign	0.0	-0.47	Likely Benign	-0.35	Likely Benign	0.59	Ambiguous	0.336	Likely Benign	-4.67	Deleterious	0.985	Probably Damaging	0.832	Possibly Damaging	3.94	Benign	0.03	Affected			0.0982	0.4705		0	-1	5.8	3.02
c.70G>C	V24L 2D AIThe SynGAP1 missense variant V24L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for V24L, 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		0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-2.590	Likely Benign	0.320	Likely Benign	Likely Benign										0.053	Likely Benign	-0.62	Neutral	0.043	Benign	0.011	Benign	3.94	Benign	0.00	Affected			0.1102	0.5226		2	1	-0.4	14.03
c.70G>T	V24L 2D AIThe SynGAP1 missense variant V24L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for V24L, 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		0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-2.590	Likely Benign	0.320	Likely Benign	Likely Benign										0.053	Likely Benign	-0.62	Neutral	0.043	Benign	0.011	Benign	3.94	Benign	0.00	Affected			0.1102	0.5226		2	1	-0.4	14.03
c.74G>C	R25P 2D AIThe SynGAP1 missense variant R25P is not reported 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 uniformly 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 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 status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375											-3.394	Likely Benign	0.424	Ambiguous	Likely Benign										0.155	Likely Benign	-1.56	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	3.94	Benign	0.00	Affected			0.2217	0.4571		0	-2	2.9	-59.07
c.7A>T	R3W 2D AIThe SynGAP1 missense variant R3W is not reported 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‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R3W, 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		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875											-5.023	Likely Benign	0.591	Likely Pathogenic	Likely Benign										0.122	Likely Benign	0.08	Neutral	0.962	Probably Damaging	0.363	Benign	3.94	Benign	0.00	Affected			0.1407	0.4634		2	-3	3.6	30.03
c.89A>G	H30R 2D AIThe SynGAP1 missense variant H30R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. 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		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-2.156	Likely Benign	0.186	Likely Benign	Likely Benign										0.138	Likely Benign	-2.17	Neutral	0.462	Possibly Damaging	0.599	Possibly Damaging	3.94	Benign	0.00	Affected			0.2762	0.3590		2	0	-1.3	19.05
c.89A>T	H30L 2D AIThe SynGAP1 H30L 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, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (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 any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-2.073	Likely Benign	0.117	Likely Benign	Likely Benign										0.163	Likely Benign	-2.88	Deleterious	0.462	Possibly Damaging	0.599	Possibly Damaging	3.94	Benign	0.00	Affected			0.1523	0.5793		-2	-3	7.0	-23.98
c.109T>A	S37T 2D AIThe SynGAP1 missense variant S37T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-3.854	Likely Benign	0.134	Likely Benign	Likely Benign										0.062	Likely Benign	-0.60	Neutral	0.140	Benign	0.481	Possibly Damaging	3.95	Benign	0.00	Affected			0.2093	0.5974		1	1	0.1	14.03
c.143T>C	F48S 2D AIThe SynGAP1 missense variant F48S has no ClinVar assertion and is not reported in gnomAD. High‑accuracy predictors: AlphaMissense‑Optimized returned an uncertain classification; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect; Foldetta predictions are unavailable. Among the remaining tools, six predict benign (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM) while two predict pathogenic (SIFT, AlphaMissense‑Default). Based on the aggregate predictions, the variant is most likely benign; this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-6.382	Likely Benign	0.916	Likely Pathogenic	Ambiguous										0.214	Likely Benign	-2.25	Neutral	0.334	Benign	0.099	Benign	3.95	Benign	0.00	Affected			0.4577	0.0901		-3	-2	-3.6	-60.10
c.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.2330T>A	L777H 2D AIThe SynGAP1 missense variant L777H has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence—including the consensus of high‑accuracy tools—suggests that the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-6.719	Likely Benign	0.492	Ambiguous	Likely Benign										0.230	Likely Benign	-2.51	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	3.95	Benign	0.00	Affected			0.1052	0.0972		-2	-3	-7.0	23.98
c.241C>A	L81M 2D AIThe SynGAP1 missense variant L81M is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33425849‑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 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 result is available. Overall, the majority of evidence points to a benign impact, 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		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250								6-33425849-C-A	1	6.20e-7	-5.351	Likely Benign	0.254	Likely Benign	Likely Benign										0.039	Likely Benign	-0.27	Neutral	0.789	Possibly Damaging	0.165	Benign	3.95	Benign	0.00	Affected	4.32	1	0.0692	0.2432		2	4	-1.9	18.03
c.2735C>T	T912I 2D AIThe SynGAP1 missense variant T912I is listed in gnomAD (ID 6‑33443287‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no available result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data is missing. Overall, the majority of reliable predictors indicate a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250								6-33443287-C-T	2	1.24e-6	-4.461	Likely Benign	0.522	Ambiguous	Likely Benign										0.117	Likely Benign	-1.27	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	3.95	Benign	0.00	Affected	3.77	5	0.0945	0.5615		-1	0	5.2	12.05
c.274G>T	G92W 2D AIThe SynGAP1 missense variant G92W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) suggest a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.575842	Disordered	0.537848	Binding	0.337	0.874	0.625											-6.502	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.224	Likely Benign	-2.61	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	3.95	Benign	0.00	Affected			0.0640	0.4546		-7	-2	-0.5	129.16
c.2942G>C	G981A 2D AIThe SynGAP1 missense variant G981A is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none reported). 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											-3.374	Likely Benign	0.368	Ambiguous	Likely Benign										0.064	Likely Benign	-0.95	Neutral	0.561	Possibly Damaging	0.376	Benign	3.95	Benign	0.00	Affected			0.3512	0.4925		1	0	2.2	14.03
c.3214A>C	K1072Q 2D AIThe SynGAP1 missense variant K1072Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-1.631	Likely Benign	0.589	Likely Pathogenic	Likely Benign										0.081	Likely Benign	-0.63	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.95	Benign	0.12	Tolerated			0.4465	0.1804		1	1	0.4	-0.04
c.3217T>G	S1073A 2D AIThe SynGAP1 missense variant S1073A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign status. Foldetta’s protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that 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		0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-5.333	Likely Benign	0.220	Likely Benign	Likely Benign										0.104	Likely Benign	-0.96	Neutral	0.447	Benign	0.103	Benign	3.95	Benign	0.02	Affected			0.4571	0.5883		1	1	2.6	-16.00
c.32G>A	G11E 2D AIThe SynGAP1 missense variant G11E is reported in gnomAD (variant ID 6-33420296‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus itself is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign variant, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.501027	Binding	0.348	0.915	0.375								6-33420296-G-A	5	3.24e-6	-4.206	Likely Benign	0.219	Likely Benign	Likely Benign										0.109	Likely Benign	0.09	Neutral	0.000	Benign	0.000	Benign	3.95	Benign	0.00	Affected	4.32	1	0.1444	0.4628		-2	0	-3.1	72.06
c.341A>C	K114T 2D AIThe SynGAP1 missense variant K114T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively indicate a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM‑Consensus score is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.366	Likely Benign	0.804	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-1.48	Neutral	0.759	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.2796	0.3391		0	-1	3.2	-27.07
c.342G>C	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.342G>T	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.376T>A	F126I 2D AIThe SynGAP1 missense variant F126I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify it as benign. Only two tools predict pathogenicity—SIFT and AlphaMissense‑Default. High‑accuracy consensus methods reinforce the benign assessment: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and AlphaMissense‑Optimized itself predicts benign. The protein‑folding stability predictor Foldetta was not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-2.919	Likely Benign	0.735	Likely Pathogenic	Likely Benign										0.044	Likely Benign	-2.20	Neutral	0.160	Benign	0.045	Benign	3.95	Benign	0.00	Affected			0.2569	0.2418		1	0	1.7	-34.02
c.3946A>C	N1316H 2D AIThe SynGAP1 missense variant N1316H is reported in gnomAD (ID 6‑33451820‑A‑C) but 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, also indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned to the variant. 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-C			-4.151	Likely Benign	0.247	Likely Benign	Likely Benign										0.069	Likely Benign	-1.87	Neutral	0.939	Possibly Damaging	0.496	Possibly Damaging	3.95	Benign	0.00	Affected	3.77	5	0.1535	0.6636		1	2	0.3	23.04
c.3967C>A	P1323T 2D AIThe SynGAP1 missense variant P1323T is reported in gnomAD (ID 6‑33451841‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. Only two algorithms—polyPhen‑2 HumDiv and SIFT—suggest a damaging impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with any ClinVar classification, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875								6-33451841-C-A			-6.296	Likely Benign	0.073	Likely Benign	Likely Benign										0.064	Likely Benign	-0.37	Neutral	0.588	Possibly Damaging	0.227	Benign	3.95	Benign	0.00	Affected	4.32	1	0.1988	0.5161		-1	0	0.9	3.99
c.3989A>G	Q1330R 2D AIThe SynGAP1 missense variant Q1330R is listed in gnomAD (ID 6‑33451863‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote 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; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875								6-33451863-A-G			-3.601	Likely Benign	0.472	Ambiguous	Likely Benign										0.031	Likely Benign	-1.65	Neutral	0.898	Possibly Damaging	0.341	Benign	3.95	Benign	0.03	Affected	3.77	5	0.1349	0.2333		1	1	-1.0	28.06
c.430A>G	T144A 2D AIThe SynGAP1 missense variant T144A is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, 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		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-4.007	Likely Benign	0.440	Ambiguous	Likely Benign										0.065	Likely Benign	-2.24	Neutral	0.000	Benign	0.001	Benign	3.95	Benign	0.00	Affected			0.4777	0.4131		1	0	2.5	-30.03
c.481C>G	P161A 2D AIThe SynGAP1 missense variant P161A is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. When predictions are grouped by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the balance of evidence, especially the SGM Consensus and the majority of individual predictors, indicates that P161A 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		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-9.012	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous										0.079	Likely Benign	-3.52	Deleterious	0.247	Benign	0.091	Benign	3.95	Benign	0.00	Affected			0.3600	0.4123		1	-1	3.4	-26.04
c.514C>T	R172W 2D AIThe SynGAP1 missense variant R172W is listed in ClinVar (ID 996892.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33435156‑C‑T). Prediction tools that agree on a benign effect include REVEL and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic.” AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no definitive stabilizing‑folding evidence. Overall, the majority of computational predictions support a pathogenic classification, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375					Uncertain		2	6-33435156-C-T	9	5.58e-6	-10.258	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous										0.228	Likely Benign	-3.61	Deleterious	0.997	Probably Damaging	0.803	Possibly Damaging	3.95	Benign	0.00	Affected	3.61	5	0.1071	0.4065		2	-3	3.6	30.03
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.631A>C	S211R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a pathogenic signal is reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of tools predict a pathogenic effect, and the high‑accuracy predictions reinforce this conclusion. 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	PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-14.126	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.49	Likely Benign	1.0	0.20	Likely Benign	0.35	Likely Benign	0.97	Ambiguous	0.132	Likely Benign	-4.00	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.95	Benign	0.02	Affected			0.1003	0.3592		0	-1	-3.7	69.11
c.632G>A	S211N 2D AIThe SynGAP1 S211N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and premPS. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the overall prediction leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.995	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	0.60	Ambiguous	1.2	1.39	Ambiguous	1.00	Ambiguous	1.21	Destabilizing	0.174	Likely Benign	-2.22	Neutral	0.982	Probably Damaging	0.747	Possibly Damaging	3.95	Benign	0.09	Tolerated			0.1534	0.4863		1	1	-2.7	27.03
c.632G>C	S211T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211T is not 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, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Two tools, FoldX and Rosetta, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-10.301	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign	0.98	Ambiguous	0.5	-0.78	Ambiguous	0.10	Likely Benign	0.50	Likely Benign	0.157	Likely Benign	-2.33	Neutral	0.948	Possibly Damaging	0.484	Possibly Damaging	3.95	Benign	0.07	Tolerated			0.1678	0.5960		1	1	0.1	14.03
c.633C>A	S211R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, FATHMM, and Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” The premPS score is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions and the two high‑accuracy pathogenic calls suggest that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-14.126	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.49	Likely Benign	1.0	0.20	Likely Benign	0.35	Likely Benign	0.97	Ambiguous	0.144	Likely Benign	-4.00	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.95	Benign	0.02	Affected			0.1003	0.3592		0	-1	-3.7	69.11
c.633C>G	S211R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, FATHMM, and the protein‑stability integrator Foldetta, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and premPS is uncertain. High‑accuracy assessments give conflicting signals: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus also predicts Likely Pathogenic, but Foldetta, which combines FoldX‑MD and Rosetta outputs, predicts Benign. Overall, the majority of tools and the consensus score point 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	PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-14.126	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.49	Likely Benign	1.0	0.20	Likely Benign	0.35	Likely Benign	0.97	Ambiguous	0.144	Likely Benign	-4.00	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.95	Benign	0.02	Affected			0.1003	0.3592		0	-1	-3.7	69.11
c.73C>G	R25G 2D AIThe SynGAP1 missense variant R25G is not reported in ClinVar and is absent from 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 and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. When high‑accuracy tools are considered separately, AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome, and Foldetta data are unavailable. Overall, the majority of robust predictors lean toward a benign interpretation. 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		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375											-3.533	Likely Benign	0.373	Ambiguous	Likely Benign										0.122	Likely Benign	-1.69	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	3.95	Benign	0.00	Affected			0.3621	0.3572		-3	-2	4.1	-99.14
c.116A>G	Y39C 2D AIThe SynGAP1 missense variant Y39C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-3.109	Likely Benign	0.123	Likely Benign	Likely Benign										0.203	Likely Benign	-2.00	Neutral	0.943	Possibly Damaging	0.941	Probably Damaging	3.96	Benign	0.00	Affected			0.3007	0.2849		0	-2	3.8	-60.04
c.1217A>T	Y406F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the variant as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-3.427	Likely Benign	0.080	Likely Benign	Likely Benign	-0.01	Likely Benign	0.2	0.40	Likely Benign	0.20	Likely Benign	0.15	Likely Benign	0.079	Likely Benign	-0.93	Neutral	0.002	Benign	0.002	Benign	3.96	Benign	0.31	Tolerated			0.2673	0.3952		7	3	4.1	-16.00
c.1219C>A	Q407K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Two tools, FoldX and premPS, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is unavailable because FoldX is uncertain and Rosetta alone is benign. Overall, the majority of evidence points to a pathogenic impact for Q407K. This conclusion is not contradicted by ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-14.893	Likely Pathogenic	0.765	Likely Pathogenic	Likely Benign	0.61	Ambiguous	0.1	0.19	Likely Benign	0.40	Likely Benign	0.93	Ambiguous	0.246	Likely Benign	-3.42	Deleterious	0.863	Possibly Damaging	0.773	Possibly Damaging	3.96	Benign	0.07	Tolerated			0.1656	0.3504		1	1	-0.4	0.04
c.1219C>G	Q407E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome. AlphaMissense‑Default, FoldX, Rosetta, and Foldetta 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 tools and the SGM Consensus support a pathogenic classification, while a minority predict benign. No ClinVar entry exists to contradict these predictions. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-12.631	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.50	Ambiguous	0.1	1.68	Ambiguous	1.09	Ambiguous	1.30	Destabilizing	0.243	Likely Benign	-2.66	Deleterious	0.989	Probably Damaging	0.930	Probably Damaging	3.96	Benign	0.03	Affected			0.1199	0.2000		2	2	0.0	0.98
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.179A>C	D60A 2D AIThe SynGAP1 D60A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates 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 evaluated tools lean toward a benign interpretation, with no evidence of pathogenicity from the high‑confidence methods. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none exists for this allele. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-4.500	Likely Benign	0.918	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-2.17	Neutral	0.909	Possibly Damaging	0.857	Possibly Damaging	3.96	Benign	0.00	Affected			0.3851	0.7405		0	-2	5.3	-44.01
c.2564T>A	L855H 2D AIThe SynGAP1 missense variant L855H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-3.224	Likely Benign	0.148	Likely Benign	Likely Benign										0.114	Likely Benign	-2.07	Neutral	0.938	Possibly Damaging	0.690	Possibly Damaging	3.96	Benign	0.01	Affected			0.1137	0.1313		-2	-3	-7.0	23.98
c.2735C>A	T912N 2D AIThe SynGAP1 missense variant T912N is listed in ClinVar with an uncertain significance (ClinVar ID 2337624.0) 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, 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 (FoldX‑MD/Rosetta) stability result is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250					Uncertain		1				-4.260	Likely Benign	0.190	Likely Benign	Likely Benign										0.116	Likely Benign	-1.15	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	3.96	Benign	0.00	Affected	3.77	5	0.1095	0.3750		0	0	-2.8	13.00
c.277C>T	R93W 2D AIThe SynGAP1 missense variant R93W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R93W, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.549151	Binding	0.290	0.874	0.625											-5.652	Likely Benign	0.514	Ambiguous	Likely Benign										0.094	Likely Benign	-2.22	Neutral	0.981	Probably Damaging	0.257	Benign	3.96	Benign	0.00	Affected			0.1413	0.3835		2	-3	3.6	30.03
c.2911C>A	P971T 2D AIThe SynGAP1 missense variant P971T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625											-5.627	Likely Benign	0.053	Likely Benign	Likely Benign										0.053	Likely Benign	-0.95	Neutral	0.001	Benign	0.003	Benign	3.96	Benign	0.00	Affected			0.1388	0.5888		0	-1	0.9	3.99
c.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.3214A>G	K1072E 2D AIThe SynGAP1 missense variant K1072E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments indicate that AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (derived from the same set of predictors) labels it as likely benign. No Foldetta stability analysis is available for this residue. Overall, the majority of tools lean toward a benign effect, but the presence of pathogenic calls from several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of evidence, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-3.889	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-0.90	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.96	Benign	0.08	Tolerated			0.3636	0.1874		0	1	0.4	0.94
c.3238G>C	A1080P 2D AIThe SynGAP1 missense variant A1080P is not reported 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 (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for A1080P, 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		0.912647	Disordered	0.981457	Binding	0.303	0.900	0.750											-2.429	Likely Benign	0.254	Likely Benign	Likely Benign										0.170	Likely Benign	-1.15	Neutral	0.996	Probably Damaging	0.833	Possibly Damaging	3.96	Benign	0.02	Affected			0.1884	0.5324		1	-1	-3.4	26.04
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.335G>A	G112E 2D AIThe SynGAP1 missense variant G112E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta predictions are not available. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. 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.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-3.470	Likely Benign	0.818	Likely Pathogenic	Ambiguous										0.134	Likely Benign	-3.30	Deleterious	0.421	Benign	0.146	Benign	3.96	Benign	0.00	Affected			0.1330	0.3814		0	-2	-3.1	72.06
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.377T>C	F126S 2D AIThe SynGAP1 missense variant F126S is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic effect. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” Overall, the majority of high‑accuracy tools (REVEL, PROVEAN, polyPhen‑2, ESM1b, FATHMM, and SGM‑Consensus) support a benign interpretation, while only two tools (SIFT, AlphaMissense‑Default) suggest pathogenicity. Given the preponderance of benign predictions and the absence of ClinVar evidence, 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		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.234	Likely Benign	0.844	Likely Pathogenic	Ambiguous										0.086	Likely Benign	-2.46	Neutral	0.160	Benign	0.045	Benign	3.96	Benign	0.00	Affected			0.4833	0.0000		-3	-2	-3.6	-60.10
c.3946A>G	N1316D 2D AIThe SynGAP1 missense variant N1316D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451820‑A‑G). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT, 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) also leans toward benign, with two benign and one pathogenic prediction among the four considered. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750								6-33451820-A-G			-2.717	Likely Benign	0.364	Ambiguous	Likely Benign										0.057	Likely Benign	-2.80	Deleterious	0.225	Benign	0.084	Benign	3.96	Benign	0.00	Affected	3.77	5	0.2095	0.3745		1	2	0.0	0.98
c.3947A>C	N1316T 2D AIThe SynGAP1 missense variant N1316T is reported in gnomAD (ID 6‑33451821‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. When predictions are grouped by consensus, the benign‑predicating tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750								6-33451821-A-C			-3.080	Likely Benign	0.315	Likely Benign	Likely Benign										0.107	Likely Benign	-3.18	Deleterious	0.127	Benign	0.045	Benign	3.96	Benign	0.00	Affected	3.77	5	0.1450	0.6621		0	0	2.8	-13.00
c.467T>A	F156Y 2D AIThe SynGAP1 missense variant F156Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas a majority of tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a tie (2 pathogenic vs. 2 benign) and thus unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (5 pathogenic vs. 3 benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-11.811	Likely Pathogenic	0.869	Likely Pathogenic	Ambiguous										0.136	Likely Benign	-1.51	Neutral	0.981	Probably Damaging	0.931	Probably Damaging	3.96	Benign	0.00	Affected			0.1363	0.1419		7	3	-4.1	16.00
c.494G>T	S165I 2D AISynGAP1 missense variant S165I has no ClinVar record and is absent from gnomAD. Individual prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the majority of single‑tool predictions favor a benign effect, whereas the consensus score suggests pathogenicity. Consequently, the variant is most likely benign according to the bulk of 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		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-11.304	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign										0.259	Likely Benign	-2.53	Deleterious	0.084	Benign	0.031	Benign	3.96	Benign	0.00	Affected			0.0943	0.5027		-1	-2	5.3	26.08
c.499G>A	D167N 2D AIThe SynGAP1 missense variant D167N is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33432796‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely benign; 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.			0.429200	Structured	0.502306	Binding	0.377	0.667	0.375								6-33432796-G-A	3	1.86e-6	-11.939	Likely Pathogenic	0.843	Likely Pathogenic	Ambiguous										0.097	Likely Benign	-2.32	Neutral	0.141	Benign	0.123	Benign	3.96	Benign	0.00	Affected	3.74	4	0.1222	0.7330		1	2	0.0	-0.98
c.517C>A	L173M 2D AIThe SynGAP1 missense variant L173M is not 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—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 yields two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence favors a benign classification, 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.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-7.149	In-Between	0.534	Ambiguous	Likely Benign										0.129	Likely Benign	-0.61	Neutral	0.940	Possibly Damaging	0.564	Possibly Damaging	3.96	Benign	0.20	Tolerated			0.0648	0.3123		4	2	-1.9	18.03
c.574G>A	A192T 2D AIThe SynGAP1 missense variant A192T has no ClinVar record (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, 1 uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-7.562	In-Between	0.958	Likely Pathogenic	Likely Pathogenic										0.089	Likely Benign	-2.46	Neutral	0.978	Probably Damaging	0.714	Possibly Damaging	3.96	Benign	0.34	Tolerated			0.1148	0.5343		1	0	-2.5	30.03
c.581A>G	E194G 2D AIThe SynGAP1 missense variant E194G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-9.136	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.316	Likely Benign	-4.47	Deleterious	0.580	Possibly Damaging	0.196	Benign	3.96	Benign	0.01	Affected			0.3633	0.4616		0	-2	3.1	-72.06
c.605A>T	E202V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E202V missense variant has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SIFT, PROVEAN, polyPhen‑2 HumDiv, ESM1b, 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 benign. Because the majority of tools (8 benign vs. 5 pathogenic) lean toward a benign outcome, the variant is most likely benign, although the SGM Consensus suggests pathogenicity. 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	PH	0.363090	Structured	0.429450	Uncertain	0.712	0.415	0.125											-8.990	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.48	Likely Benign	0.0	0.34	Likely Benign	0.41	Likely Benign	0.12	Likely Benign	0.270	Likely Benign	-4.81	Deleterious	0.649	Possibly Damaging	0.259	Benign	3.96	Benign	0.01	Affected			0.0525	0.7007		-2	-2	7.7	-29.98
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.70G>A	V24I 2D AIThe SynGAP1 missense variant V24I is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6-33423479-G-A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the overwhelming majority of computational evidence supports a benign impact for V24I, and this conclusion does not contradict the ClinVar designation, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500					Uncertain		1	6-33423479-G-A	9	5.58e-6	-3.701	Likely Benign	0.137	Likely Benign	Likely Benign										0.069	Likely Benign	-0.25	Neutral	0.043	Benign	0.031	Benign	3.96	Benign	0.00	Affected	4.32	1	0.0844	0.4564		3	4	0.3	14.03
c.8G>T	R3M 2D AIThe SynGAP1 missense variant R3M is not reported 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 high‑accuracy consensus methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and Foldetta data are unavailable. Overall, the majority of evidence supports a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875											-4.655	Likely Benign	0.618	Likely Pathogenic	Likely Benign										0.097	Likely Benign	0.00	Neutral	0.872	Possibly Damaging	0.162	Benign	3.96	Benign	0.00	Affected			0.1906	0.4795		0	-1	6.4	-24.99
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.92G>C	R31P 2D AIThe SynGAP1 missense variant R31P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign impact for R31P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.437905	Uncertain	0.324	0.878	0.250											-3.185	Likely Benign	0.300	Likely Benign	Likely Benign										0.209	Likely Benign	-1.64	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	3.96	Benign	0.00	Affected			0.2220	0.5005		0	-2	2.9	-59.07
c.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.2376A>C	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2376A>T	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-3.746	Likely Benign	0.089	Likely Benign	Likely Benign										0.091	Likely Benign	-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			0.2096	0.5376		3	2	0.0	-14.03
c.2564T>C	L855P 2D AIThe SynGAP1 missense variant L855P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-2.434	Likely Benign	0.092	Likely Benign	Likely Benign										0.116	Likely Benign	-1.19	Neutral	0.586	Possibly Damaging	0.377	Benign	3.97	Benign	0.14	Tolerated			0.3633	0.1805		-3	-3	-5.4	-16.04
c.2668C>G	R890G 2D AIThe SynGAP1 missense variant R890G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that R890G 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		0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.080	Likely Benign	0.310	Likely Benign	Likely Benign										0.146	Likely Benign	-1.99	Neutral	0.990	Probably Damaging	0.894	Possibly Damaging	3.97	Benign	0.33	Tolerated			0.3734	0.2711		-3	-2	4.1	-99.14
c.2669G>A	R890H 2D AIThe SynGAP1 missense variant R890H is listed in ClinVar as a benign alteration (ClinVar ID 1037885.0) and is observed in gnomAD (6‑33443221‑G‑A). All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and no tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” while Foldetta’s protein‑folding stability analysis is unavailable. Overall, the computational evidence strongly supports a benign classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625					Benign		1	6-33443221-G-A	19	1.18e-5	-3.600	Likely Benign	0.198	Likely Benign	Likely Benign										0.056	Likely Benign	-1.29	Neutral	0.254	Benign	0.134	Benign	3.97	Benign	0.15	Tolerated	4.32	4	0.3032	0.1235		2	0	1.3	-19.05
c.314C>G	S105W 2D AIThe SynGAP1 missense variant S105W is catalogued in gnomAD (ID 6‑33432179‑C‑G) but has no ClinVar entry. 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, reports a “Likely Benign” status, reflecting the majority of benign calls. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also leans benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that 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		0.788093	Disordered	0.669201	Binding	0.364	0.870	0.625								6-33432179-C-G	2	1.24e-6	-5.600	Likely Benign	0.606	Likely Pathogenic	Likely Benign										0.177	Likely Benign	-2.28	Neutral	0.998	Probably Damaging	0.844	Possibly Damaging	3.97	Benign	0.00	Affected	4.32	1	0.0705	0.4984		-3	-2	-0.1	99.14
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.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.467T>C	F156S 2D AIThe SynGAP1 missense variant F156S 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 predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from the same set of high‑accuracy predictors) 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 is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-14.082	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.62	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	3.97	Benign	0.00	Affected			0.5183	0.0200	Weaken	-3	-2	-3.6	-60.10
c.500A>C	D167A 2D AIThe SynGAP1 D167A missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools split evenly: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the preponderance of evidence, especially the SGM Consensus, points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database status. 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											-13.473	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.61	Deleterious	0.141	Benign	0.056	Benign	3.97	Benign	0.00	Affected			0.3429	0.6549		0	-2	5.3	-44.01
c.536A>G	E179G 2D AIThe SynGAP1 missense variant E179G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Among the available in‑silico predictors, six tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM) unanimously predict a benign effect, whereas two tools (PROVEAN and AlphaMissense‑Default) predict pathogenicity. High‑accuracy predictors give no definitive verdict: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes); and Foldetta results are unavailable. Consequently, the overall evidence leans toward a benign interpretation, with no conflict with the lack of ClinVar annotation. 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.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-6.527	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.158	Likely Benign	-4.24	Deleterious	0.001	Benign	0.004	Benign	3.97	Benign	0.09	Tolerated			0.3273	0.6425		0	-2	3.1	-72.06
c.537G>C	E179D 2D AIThe SynGAP1 missense variant E179D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote, and Foldetta data are unavailable. Overall, the balance of evidence (four benign vs. three pathogenic predictions, with a benign consensus from high‑accuracy methods) indicates that the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-7.741	In-Between	0.929	Likely Pathogenic	Ambiguous										0.145	Likely Benign	-1.91	Neutral	0.596	Possibly Damaging	0.142	Benign	3.97	Benign	0.05	Affected			0.2327	0.5011		3	2	0.0	-14.03
c.537G>T	E179D 2D AIThe SynGAP1 missense variant E179D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote, and Foldetta data are unavailable. Overall, the balance of evidence (four benign vs. three pathogenic predictions, with a benign consensus from high‑accuracy methods) indicates that the variant is most likely benign. 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.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-7.741	In-Between	0.929	Likely Pathogenic	Ambiguous										0.145	Likely Benign	-1.91	Neutral	0.596	Possibly Damaging	0.142	Benign	3.97	Benign	0.05	Affected			0.2327	0.5011		3	2	0.0	-14.03
c.74G>T	R25L 2D AIThe SynGAP1 missense variant R25L is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic impact. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight a benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta data are missing. Taken together, the majority of robust predictors and the consensus analysis support a benign classification for R25L. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375											-3.443	Likely Benign	0.484	Ambiguous	Likely Benign										0.121	Likely Benign	-1.59	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	3.97	Benign	0.00	Affected			0.2045	0.4792		-3	-2	8.3	-43.03
c.91C>G	R31G 2D AIThe SynGAP1 missense variant R31G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for R31G, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.437905	Uncertain	0.324	0.878	0.250											-3.259	Likely Benign	0.269	Likely Benign	Likely Benign										0.141	Likely Benign	-1.77	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	3.97	Benign	0.00	Affected			0.3389	0.3942		-3	-2	4.1	-99.14
c.109T>G	S37A 2D AIThe SynGAP1 missense variant S37A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500											-4.052	Likely Benign	0.125	Likely Benign	Likely Benign										0.045	Likely Benign	-0.86	Neutral	0.140	Benign	0.355	Benign	3.98	Benign	0.00	Affected			0.5089	0.4970	Weaken	1	1	2.6	-16.00
c.115T>G	Y39D 2D AIThe SynGAP1 missense variant Y39D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for Y39D, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-2.338	Likely Benign	0.333	Likely Benign	Likely Benign										0.166	Likely Benign	-1.86	Neutral	0.824	Possibly Damaging	0.828	Possibly Damaging	3.98	Benign	0.00	Affected			0.4099	0.0903		-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.187G>A	E63K 2D AIThe SynGAP1 E63K missense variant (ClinVar ID 2830630.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict a pathogenic outcome. AlphaMissense‑Optimized is inconclusive, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. Overall, the high‑accuracy consensus leans toward a benign effect, and this assessment does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125					Uncertain		1				-4.976	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-0.70	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	0.1995	0.7261		1	0	-0.4	-0.94
c.189G>C	E63D 2D AIThe SynGAP1 missense variant E63D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also reports it as likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a benign 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 Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.821	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.066	Likely Benign	-0.83	Neutral	0.267	Benign	0.585	Possibly Damaging	3.98	Benign	0.00	Affected			0.1524	0.4130		3	2	0.0	-14.03
c.189G>T	E63D 2D AIThe SynGAP1 missense variant E63D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also indicates benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective evidence points to a benign effect for E63D, 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		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.821	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.066	Likely Benign	-0.83	Neutral	0.267	Benign	0.585	Possibly Damaging	3.98	Benign	0.00	Affected			0.1524	0.4130		3	2	0.0	-14.03
c.217A>T	R73W 2D AIThe SynGAP1 missense variant R73W is not reported 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 a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.453164	Uncertain	0.332	0.826	0.375											-5.874	Likely Benign	0.318	Likely Benign	Likely Benign										0.109	Likely Benign	-1.96	Neutral	0.962	Probably Damaging	0.274	Benign	3.98	Benign	0.00	Affected			0.1505	0.4035		2	-3	3.6	30.03
c.2329C>T	L777F 2D AIThe SynGAP1 missense variant L777F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-4.499	Likely Benign	0.175	Likely Benign	Likely Benign										0.115	Likely Benign	-1.91	Neutral	0.968	Probably Damaging	0.966	Probably Damaging	3.98	Benign	0.01	Affected			0.0697	0.3576		2	0	-1.0	34.02
c.2669G>T	R890L 2D AIThe SynGAP1 missense variant R890L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign prediction (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy and consensus predictions indicate a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.387	Likely Benign	0.389	Ambiguous	Likely Benign										0.213	Likely Benign	-2.74	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	3.98	Benign	0.20	Tolerated			0.1876	0.3406		-3	-2	8.3	-43.03
c.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.273G>C	E91D 2D AIThe SynGAP1 missense variant E91D is reported in gnomAD (variant ID 6‑33425881‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500								6-33425881-G-C	1	6.20e-7	-3.160	Likely Benign	0.293	Likely Benign	Likely Benign										0.095	Likely Benign	-0.84	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	0.2000	0.5219		2	3	0.0	-14.03
c.273G>T	E91D 2D AIThe SynGAP1 missense variant E91D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to 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		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-3.160	Likely Benign	0.293	Likely Benign	Likely Benign										0.095	Likely Benign	-0.84	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	0.2000	0.5219		2	3	0.0	-14.03
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.3232G>A	V1078I 2D AIThe SynGAP1 missense variant V1078I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods suggests that V1078I 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		0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750											-3.652	Likely Benign	0.200	Likely Benign	Likely Benign										0.120	Likely Benign	-0.16	Neutral	0.625	Possibly Damaging	0.266	Benign	3.98	Benign	0.07	Tolerated			0.0771	0.4693		4	3	0.3	14.03
c.340A>C	K114Q 2D AIThe SynGAP1 missense variant K114Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.221	Likely Benign	0.467	Ambiguous	Likely Benign										0.058	Likely Benign	-1.33	Neutral	0.608	Possibly Damaging	0.108	Benign	3.98	Benign	0.00	Affected			0.5476	0.1530	Weaken	1	1	0.4	-0.04
c.352A>G	M118V 2D AIThe SynGAP1 missense variant M118V is not reported 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		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-2.322	Likely Benign	0.122	Likely Benign	Likely Benign										0.158	Likely Benign	-1.23	Neutral	0.012	Benign	0.011	Benign	3.98	Benign	0.02	Affected			0.3326	0.3630		2	1	2.3	-32.06
c.376T>G	F126V 2D AIThe SynGAP1 missense variant F126V is not reported 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 F126V, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-1.584	Likely Benign	0.635	Likely Pathogenic	Likely Benign										0.086	Likely Benign	-2.47	Neutral	0.160	Benign	0.045	Benign	3.98	Benign	0.00	Affected			0.2496	0.2646		-1	-1	1.4	-48.04
c.3953T>C	L1318P 2D AIThe SynGAP1 missense variant L1318P is listed in gnomAD (ID 6‑33451827‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.968271	Binding	0.399	0.865	0.750								6-33451827-T-C			-2.307	Likely Benign	0.116	Likely Benign	Likely Benign										0.126	Likely Benign	-2.90	Deleterious	0.813	Possibly Damaging	0.212	Benign	3.98	Benign	0.00	Affected	3.77	5	0.3424	0.1411		-3	-3	-5.4	-16.04
c.3988C>A	Q1330K 2D AIThe SynGAP1 missense variant Q1330K is catalogued in gnomAD (ID 6‑33451862‑C‑A) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status, reflecting the majority of benign predictions. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence—including the high‑accuracy tools—suggests that Q1330K 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		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875								6-33451862-C-A			-4.120	Likely Benign	0.605	Likely Pathogenic	Likely Benign										0.027	Likely Benign	-1.52	Neutral	0.544	Possibly Damaging	0.259	Benign	3.98	Benign	0.04	Affected	3.77	5	0.1607	0.4127		1	1	-0.4	0.04
c.3988C>G	Q1330E 2D AIThe SynGAP1 missense variant Q1330E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875											-3.428	Likely Benign	0.281	Likely Benign	Likely Benign										0.035	Likely Benign	-1.12	Neutral	0.613	Possibly Damaging	0.240	Benign	3.98	Benign	0.06	Tolerated			0.1346	0.2409		2	2	0.0	0.98
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.475A>G	I159V 2D AIThe SynGAP1 I159V 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus (2 benign vs. 1 pathogenic, with one uncertain). Foldetta results are unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. 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											-9.714	Likely Pathogenic	0.384	Ambiguous	Likely Benign										0.113	Likely Benign	-0.25	Neutral	0.803	Possibly Damaging	0.847	Possibly Damaging	3.98	Benign	0.00	Affected			0.1111	0.2736		4	3	-0.3	-14.03
c.514C>G	R172G 2D AIThe SynGAP1 R172G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Computational predictions are split: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy consensus tools are inconclusive: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 split, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic according to current predictions, and there is no ClinVar annotation to contradict this ambiguous assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375											-6.685	Likely Benign	0.811	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-2.69	Deleterious	0.789	Possibly Damaging	0.253	Benign	3.98	Benign	0.02	Affected			0.2991	0.3169		-3	-2	4.1	-99.14
c.533A>G	K178R 2D AIThe SynGAP1 missense variant K178R is reported in gnomAD (ID 6‑33435175‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus also indicates likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for K178R, 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		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375								6-33435175-A-G	1	6.20e-7	-4.398	Likely Benign	0.281	Likely Benign	Likely Benign										0.117	Likely Benign	-1.62	Neutral	0.905	Possibly Damaging	0.393	Benign	3.98	Benign	0.14	Tolerated	3.54	6	0.5403	0.1131	Weaken	2	3	-0.6	28.01
c.574G>T	A192S 2D AIThe SynGAP1 missense variant A192S is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-7.969	In-Between	0.757	Likely Pathogenic	Likely Benign										0.118	Likely Benign	-2.01	Neutral	0.633	Possibly Damaging	0.171	Benign	3.98	Benign	0.12	Tolerated			0.2365	0.3764		1	1	-2.6	16.00
c.599T>G	L200W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L200W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Foldetta) predict a pathogenic impact. Two tools (AlphaMissense‑Optimized and Rosetta) provide inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as Pathogenic, the latter integrating stability predictions from FoldX‑MD and Rosetta. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-11.550	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous	2.90	Destabilizing	1.0	1.95	Ambiguous	2.43	Destabilizing	1.20	Destabilizing	0.200	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.970	Probably Damaging	3.98	Benign	0.02	Affected			0.0627	0.2893		-2	-2	-4.7	73.05
c.607G>C	D203H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203H missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or folding result is missing or inconclusive. Overall, the predictions are mixed, but the two high‑accuracy tools favor a benign outcome, giving a slight bias toward benign. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-9.130	Likely Pathogenic	0.593	Likely Pathogenic	Likely Benign	0.00	Likely Benign	0.1	0.18	Likely Benign	0.09	Likely Benign	-0.04	Likely Benign	0.218	Likely Benign	-3.28	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	3.98	Benign	0.02	Affected			0.0962	0.4815		1	-1	0.3	22.05
c.608A>T	D203V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the SGM Consensus lean toward a pathogenic interpretation, whereas two high‑accuracy methods (AlphaMissense‑Optimized and Foldetta) suggest benign. Because ClinVar contains no entry for this variant, there is no contradiction between the predictions and existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-10.660	Likely Pathogenic	0.523	Ambiguous	Likely Benign	0.32	Likely Benign	0.0	0.44	Likely Benign	0.38	Likely Benign	0.05	Likely Benign	0.289	Likely Benign	-4.07	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	3.98	Benign	0.02	Affected			0.0534	0.4084		-2	-3	7.7	-15.96
c.621G>C	K207N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicating likely pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for K207N, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.123	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.621G>T	K207N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K207N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus (majority vote) also predicts Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence indicates that K207N is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.124	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.985C>T	R329C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R329C is reported in gnomAD (ID 6‑33437890‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, Rosetta, Foldetta, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools remain inconclusive: premPS and AlphaMissense‑Optimized. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta) as benign. Overall, six tools favor pathogenicity versus five favor benign, with one uncertain. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250								6-33437890-C-T	2	1.24e-6	-9.433	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.1	0.40	Likely Benign	0.42	Likely Benign	0.69	Ambiguous	0.313	Likely Benign	-5.70	Deleterious	0.999	Probably Damaging	0.825	Possibly Damaging	3.98	Benign	0.00	Affected	3.41	15	0.3553	0.2921		-3	-4	7.0	-53.05
c.115T>A	Y39N 2D AIThe SynGAP1 missense variant Y39N 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 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		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-3.098	Likely Benign	0.229	Likely Benign	Likely Benign										0.104	Likely Benign	-1.84	Neutral	0.824	Possibly Damaging	0.828	Possibly Damaging	3.99	Benign	0.00	Affected			0.2375	0.0903		-2	-2	-2.2	-49.07
c.118G>C	D40H 2D AIThe SynGAP1 missense variant D40H is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the consensus of available predictions 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		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-4.108	Likely Benign	0.413	Ambiguous	Likely Benign										0.147	Likely Benign	-1.28	Neutral	0.172	Benign	0.248	Benign	3.99	Benign	0.00	Affected			0.3123	0.9007		1	-1	0.3	22.05
c.142T>A	F48I 2D AIThe SynGAP1 missense variant F48I is not 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), and FATHMM, while SIFT and AlphaMissense‑Default predict a pathogenic impact. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further clarify the variant’s likely benign nature: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors benign; AlphaMissense‑Optimized remains uncertain, and Foldetta (which would evaluate protein‑folding stability) is unavailable. Overall, the balance of evidence points to a benign classification, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-7.994	In-Between	0.808	Likely Pathogenic	Ambiguous										0.108	Likely Benign	-1.67	Neutral	0.092	Benign	0.050	Benign	3.99	Benign	0.00	Affected			0.2561	0.2301		1	0	1.7	-34.02
c.23T>A	I8N 2D AIThe SynGAP1 missense variant I8N is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of predictors, including the high‑accuracy methods, points to a benign impact. This conclusion is consistent with the absence of any ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.543080	Binding	0.341	0.916	0.625											-3.979	Likely Benign	0.163	Likely Benign	Likely Benign										0.120	Likely Benign	0.05	Neutral	0.561	Possibly Damaging	0.032	Benign	3.99	Benign	0.00	Affected			0.0803	0.0540		-2	-3	-8.0	0.94
c.2576G>A	S859N 2D AIThe SynGAP1 missense variant S859N is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.184	Likely Pathogenic	0.225	Likely Benign	Likely Benign										0.142	Likely Benign	-0.62	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	3.99	Benign	0.29	Tolerated			0.1221	0.5226		1	1	-2.7	27.03
c.2576G>T	S859I 2D AIThe SynGAP1 missense variant S859I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar record exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.342	Likely Pathogenic	0.351	Ambiguous	Likely Benign										0.256	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	3.99	Benign	0.02	Affected			0.1094	0.5867		-1	-2	5.3	26.08
c.2581T>A	S861T 2D AIThe SynGAP1 missense variant S861T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. AlphaMissense‑Optimized likewise predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-4.462	Likely Benign	0.096	Likely Benign	Likely Benign										0.022	Likely Benign	-0.83	Neutral	0.043	Benign	0.026	Benign	3.99	Benign	0.14	Tolerated			0.1262	0.6245		1	1	0.1	14.03
c.277C>G	R93G 2D AIThe SynGAP1 missense variant R93G is listed in ClinVar (ID 2504251.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the same set of predictors) labels it “Likely Benign”; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that R93G is most likely benign, which 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		0.675549	Disordered	0.549151	Binding	0.290	0.874	0.625					Uncertain		1				-2.674	Likely Benign	0.400	Ambiguous	Likely Benign										0.093	Likely Benign	-1.69	Neutral	0.103	Benign	0.019	Benign	3.99	Benign	0.00	Affected	4.32	1	0.3809	0.3814		-2	-3	4.1	-99.14
c.278G>C	R93P 2D AIThe SynGAP1 missense variant R93P 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, 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 majority of evidence points to a benign effect, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.549151	Binding	0.290	0.874	0.625											-3.164	Likely Benign	0.473	Ambiguous	Likely Benign										0.121	Likely Benign	-0.32	Neutral	0.361	Benign	0.038	Benign	3.99	Benign	0.00	Affected			0.2200	0.4844		0	-2	2.9	-59.07
c.2911C>T	P971S 2D AIThe SynGAP1 missense variant P971S is catalogued in gnomAD (ID 6‑33443463‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate a benign or likely benign outcome. Only SIFT classifies the change as pathogenic, representing a minority opinion. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise reports likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625								6-33443463-C-T	1	6.20e-7	-4.188	Likely Benign	0.061	Likely Benign	Likely Benign										0.058	Likely Benign	-0.51	Neutral	0.002	Benign	0.003	Benign	3.99	Benign	0.00	Affected	4.32	2	0.3009	0.5667		-1	1	0.8	-10.04
c.310C>T	R104C 2D AIThe SynGAP1 missense variant R104C has no ClinVar entry and is present in gnomAD (ID 6‑33432175‑C‑T). 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; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.678998	Binding	0.339	0.869	0.625								6-33432175-C-T	2	1.24e-6	-5.716	Likely Benign	0.475	Ambiguous	Likely Benign										0.109	Likely Benign	-1.41	Neutral	0.993	Probably Damaging	0.446	Benign	3.99	Benign	0.00	Affected	4.32	1	0.2954	0.3292		-3	-4	7.0	-53.05																10.1016/j.ajhg.2020.11.011
c.3181G>C	G1061R 2D AIThe SynGAP1 missense variant G1061R is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification. This conclusion does not contradict ClinVar status, as the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.978672	Disordered	0.926729	Binding	0.394	0.923	0.875											-7.721	In-Between	0.343	Ambiguous	Likely Benign										0.315	Likely Benign	-0.17	Neutral	0.411	Benign	0.132	Benign	3.99	Benign	0.00	Affected			0.1037	0.4332		-3	-2	-4.1	99.14
c.3239C>T	A1080V 2D AIThe SynGAP1 missense variant A1080V is listed in gnomAD (ID 6‑33443791‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, 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		0.912647	Disordered	0.981457	Binding	0.303	0.900	0.750								6-33443791-C-T			-4.087	Likely Benign	0.229	Likely Benign	Likely Benign										0.124	Likely Benign	-1.06	Neutral	0.481	Possibly Damaging	0.144	Benign	3.99	Benign	0.04	Affected	3.77	5	0.1298	0.6056		0	0	2.4	28.05
c.3242C>G	A1081G 2D AIThe missense variant A1081G in SynGAP1 has no entry in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign. Foldetta results are unavailable. Overall, the computational evidence strongly supports a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.979759	Binding	0.288	0.895	0.750											-3.174	Likely Benign	0.191	Likely Benign	Likely Benign										0.033	Likely Benign	-1.43	Neutral	0.393	Benign	0.184	Benign	3.99	Benign	0.23	Tolerated			0.1751	0.4348		1	0	-2.2	-14.03
c.3251C>G	P1084R 2D AIThe SynGAP1 missense variant P1084R is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443803‑C‑G). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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, PROVEAN) also favors a benign outcome (2 benign vs 1 pathogenic vote). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for P1084R, and this conclusion does not contradict the ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.842060	Disordered	0.979020	Binding	0.348	0.889	1.000								6-33443803-C-G	4	2.52e-6	-4.171	Likely Benign	0.562	Ambiguous	Likely Benign										0.153	Likely Benign	-2.87	Deleterious	0.970	Probably Damaging	0.637	Possibly Damaging	3.99	Benign	0.01	Affected	3.77	5	0.1370	0.4153		-2	0	-2.9	59.07
c.354G>A	M118I 2D AIThe SynGAP1 missense variant M118I is not reported 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 the majority vote from 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 results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-3.396	Likely Benign	0.754	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-1.23	Neutral	0.005	Benign	0.004	Benign	3.99	Benign	0.02	Affected			0.1624	0.3570		2	1	2.6	-18.03
c.354G>C	M118I 2D AIThe SynGAP1 missense variant M118I is not reported 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 the majority vote from 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 results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-3.396	Likely Benign	0.754	Likely Pathogenic	Likely Benign										0.140	Likely Benign	-1.23	Neutral	0.005	Benign	0.004	Benign	3.99	Benign	0.02	Affected			0.1624	0.3570		2	1	2.6	-18.03
c.354G>T	M118I 2D AIThe SynGAP1 missense variant M118I is not reported 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 the majority vote from 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 results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-3.396	Likely Benign	0.754	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-1.23	Neutral	0.005	Benign	0.004	Benign	3.99	Benign	0.02	Affected			0.1624	0.3570		2	1	2.6	-18.03
c.392G>C	G131A 2D AIThe SynGAP1 missense variant G131A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet 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											-4.891	Likely Benign	0.512	Ambiguous	Likely Benign										0.138	Likely Benign	-2.96	Deleterious	0.620	Possibly Damaging	0.157	Benign	3.99	Benign	0.01	Affected			0.3981	0.4814		1	0	2.2	14.03
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.453C>A	D151E 2D AIThe SynGAP1 D151E variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Benign,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) 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 “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625					Uncertain		1				-5.662	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.02	Neutral	0.984	Probably Damaging	0.967	Probably Damaging	3.99	Benign	0.11	Tolerated	3.61	5	0.1494	0.7919		3	2	0.0	14.03
c.453C>G	D151E 2D AIThe SynGAP1 missense variant D151E is not reported 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 high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized remains uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for D151E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-5.662	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.02	Neutral	0.984	Probably Damaging	0.967	Probably Damaging	3.99	Benign	0.11	Tolerated	3.61	5	0.1494	0.7919		3	2	0.0	14.03
c.466T>A	F156I 2D AIThe SynGAP1 missense variant F156I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-10.505	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.38	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.99	Benign	0.00	Affected			0.1960	0.1938		1	0	1.7	-34.02
c.493A>G	S165G 2D AIThe SynGAP1 missense variant S165G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-7.691	In-Between	0.223	Likely Benign	Likely Benign										0.182	Likely Benign	-1.17	Neutral	0.272	Benign	0.086	Benign	3.99	Benign	0.00	Affected			0.2622	0.4441		1	0	0.4	-30.03
c.496G>C	A166P 2D AIThe SynGAP1 missense variant A166P is not reported 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 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 for A166P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.505037	Binding	0.384	0.658	0.125											-9.665	Likely Pathogenic	0.273	Likely Benign	Likely Benign										0.172	Likely Benign	-2.04	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	3.99	Benign	0.02	Affected			0.1861	0.3668		1	-1	-3.4	26.04
c.50C>A	S17Y 2D AIThe SynGAP1 missense variant S17Y is listed in gnomAD (ID 6‑33420314‑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‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. No Foldetta stability data are available, so it does not influence the conclusion. Overall, the majority of evidence indicates that S17Y is most likely benign, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375								6-33420314-C-A			-4.492	Likely Benign	0.551	Ambiguous	Likely Benign										0.050	Likely Benign	-1.06	Neutral	0.742	Possibly Damaging	0.047	Benign	3.99	Benign	0.00	Affected	4.32	1	0.0818	0.6366		-2	-3	-0.5	76.10
c.50C>G	S17C 2D AIThe SynGAP1 missense variant S17C 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 reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also 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		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375											-4.364	Likely Benign	0.279	Likely Benign	Likely Benign										0.044	Likely Benign	0.17	Neutral	0.486	Possibly Damaging	0.048	Benign	3.99	Benign	0.00	Affected			0.1226	0.6721		0	-1	3.3	16.06
c.50C>T	S17F 2D AIThe SynGAP1 missense variant S17F is listed in ClinVar with an “Uncertain” status (ClinVar ID 3451958.0) and is present in gnomAD (ID 6‑33420314‑C‑T). 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375					Uncertain		1	6-33420314-C-T	10	6.49e-6	-3.888	Likely Benign	0.637	Likely Pathogenic	Likely Benign										0.048	Likely Benign	-0.99	Neutral	0.486	Possibly Damaging	0.032	Benign	3.99	Benign	0.00	Affected	4.32	1	0.0729	0.6468		-2	-3	3.6	60.10
c.515G>C	R172P 2D AIThe SynGAP1 missense variant R172P has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375											-8.059	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.16	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	3.99	Benign	0.01	Affected			0.1864	0.4312		0	-2	2.9	-59.07
c.515G>T	R172L 2D AIThe SynGAP1 missense variant R172L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375											-8.201	Likely Pathogenic	0.797	Likely Pathogenic	Ambiguous										0.131	Likely Benign	-3.09	Deleterious	0.276	Benign	0.103	Benign	3.99	Benign	0.02	Affected			0.1423	0.4729		-3	-2	8.3	-43.03
c.535G>C	E179Q 2D AIThe SynGAP1 missense variant E179Q has no ClinVar record (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy consensus tools are inconclusive: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic based on current predictions, and there is no ClinVar status to contradict this ambiguous assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-10.388	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-1.82	Neutral	0.818	Possibly Damaging	0.419	Benign	3.99	Benign	0.02	Affected			0.1674	0.7383		2	2	0.0	-0.98
c.577G>C	A193P 2D AIThe SynGAP1 missense variant A193P 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 multiple independent predictors indicates that A193P 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.			0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-7.293	In-Between	0.986	Likely Pathogenic	Likely Pathogenic										0.267	Likely Benign	-2.70	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.99	Benign	0.05	Affected			0.1855	0.5601		1	-1	-3.4	26.04
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.581A>C	E194A 2D AIThe SynGAP1 missense variant E194A is not 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. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions—including the high‑accuracy tools—suggest that E194A is likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-7.101	In-Between	0.958	Likely Pathogenic	Likely Pathogenic										0.235	Likely Benign	-3.75	Deleterious	0.009	Benign	0.012	Benign	3.99	Benign	0.01	Affected			0.4331	0.5079		0	-1	5.3	-58.04
c.620A>C	K207T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K207T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; Foldetta’s stability analysis is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K207T, 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	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-11.002	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.15	Destabilizing	0.8	0.57	Ambiguous	1.36	Ambiguous	0.78	Ambiguous	0.239	Likely Benign	-4.57	Deleterious	0.982	Probably Damaging	0.747	Possibly Damaging	3.99	Benign	0.07	Tolerated			0.1636	0.4031		0	-1	3.2	-27.07
c.7A>G	R3G 2D AIThe SynGAP1 missense variant R3G is reported in gnomAD (ID 6‑33420271‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875								6-33420271-A-G			-3.093	Likely Benign	0.160	Likely Benign	Likely Benign										0.099	Likely Benign	-0.20	Neutral	0.115	Benign	0.018	Benign	3.99	Benign	0.00	Affected	4.32	1	0.3559	0.4114		-2	-3	4.1	-99.14
c.88C>T	H30Y 2D AIThe SynGAP1 H30Y missense variant (ClinVar ID 972248.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are 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 effect, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250					Uncertain		1				-3.047	Likely Benign	0.115	Likely Benign	Likely Benign										0.082	Likely Benign	-1.84	Neutral	0.273	Benign	0.478	Possibly Damaging	3.99	Benign	0.00	Affected	4.32	1	0.1572	0.4856		0	2	1.9	26.03
c.907G>A	G303R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G303R is catalogued in gnomAD (6-33437812-G-A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome; the remaining tools (FoldX, Foldetta, premPS, ESM1b) are inconclusive. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, while Foldetta remains uncertain. Taken together, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.450668	Structured	0.271087	Uncertain	0.630	0.254	0.250								6-33437812-G-A	1	6.20e-7	-7.493	In-Between	0.724	Likely Pathogenic	Likely Benign	1.44	Ambiguous	0.4	0.23	Likely Benign	0.84	Ambiguous	0.73	Ambiguous	0.048	Likely Benign	-1.38	Neutral	0.001	Benign	0.003	Benign	3.99	Benign	0.06	Tolerated	3.55	18	0.0839	0.4490		-2	-3	-4.1	99.14
c.907G>C	G303R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G303R is not 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, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome. The remaining tools—FoldX, Foldetta, premPS, and ESM1b—return uncertain or inconclusive results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, while Foldetta remains uncertain. 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 classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.450668	Structured	0.271087	Uncertain	0.630	0.254	0.250											-7.493	In-Between	0.724	Likely Pathogenic	Likely Benign	1.44	Ambiguous	0.4	0.23	Likely Benign	0.84	Ambiguous	0.73	Ambiguous	0.048	Likely Benign	-1.38	Neutral	0.001	Benign	0.003	Benign	3.99	Benign	0.06	Tolerated	3.55	18	0.0839	0.4490		-2	-3	-4.1	99.14
c.113C>A	P38Q 2D AIThe SynGAP1 missense variant P38Q is not reported 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 P38Q, 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		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375											-3.520	Likely Benign	0.183	Likely Benign	Likely Benign										0.129	Likely Benign	-2.16	Neutral	0.989	Probably Damaging	0.975	Probably Damaging	4.00	Benign	0.00	Affected			0.1737	0.5521		0	-1	-1.9	31.01
c.113C>G	P38R 2D AIThe SynGAP1 missense variant P38R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for P38R, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375											-1.799	Likely Benign	0.314	Likely Benign	Likely Benign										0.168	Likely Benign	-2.29	Neutral	0.989	Probably Damaging	0.975	Probably Damaging	4.00	Benign	0.00	Affected			0.1620	0.4060		0	-2	-2.9	59.07
c.119A>T	D40V 2D AIThe SynGAP1 missense variant D40V is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-3.350	Likely Benign	0.431	Ambiguous	Likely Benign										0.222	Likely Benign	-1.16	Neutral	0.028	Benign	0.088	Benign	4.00	Benign	0.00	Affected			0.1679	0.8357		-2	-3	7.7	-15.96
c.139C>T	R47W 2D AIThe SynGAP1 missense variant R47W is listed in ClinVar as a variant of uncertain significance and is present in the gnomAD database (ID 6‑33423548‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta results are unavailable. Overall, the majority of conventional tools suggest a pathogenic impact, but the single high‑accuracy benign prediction and the inconclusive consensus temper this view. Consequently, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment does not contradict the ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125					Uncertain		1	6-33423548-C-T	1	6.20e-7	-9.201	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-2.17	Neutral	0.994	Probably Damaging	0.919	Probably Damaging	4.00	Benign	0.00	Affected	4.32	1	0.1101	0.4158		-3	2	3.6	30.03
c.142T>G	F48V 2D AIThe SynGAP1 missense variant F48V is not reported in ClinVar and is absent from gnomAD. Consensus from routine in silico predictors shows six tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized) classifying the change as benign, while two (SIFT, AlphaMissense‑Default) predict pathogenicity; ESM1b remains uncertain. High‑accuracy assessment further supports a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote, and Foldetta data are unavailable. Consequently, the overall evidence points to a benign effect for F48V, 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.			0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-7.591	In-Between	0.756	Likely Pathogenic	Likely Benign										0.144	Likely Benign	-1.87	Neutral	0.092	Benign	0.037	Benign	4.00	Benign	0.00	Affected			0.2533	0.2300		-1	-1	1.4	-48.04
c.196C>A	P66T 2D AIThe SynGAP1 missense variant P66T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the balance of evidence leans toward a benign impact, with one high‑accuracy tool (SGM‑Consensus) supporting this view and no ClinVar entry to contradict it. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-3.373	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.139	Likely Benign	-1.81	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.00	Benign	0.00	Affected			0.1747	0.5866		0	-1	0.9	3.99
c.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.218G>T	R73M 2D AIThe SynGAP1 R73M 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 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 methods give a benign signal: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability predictor, 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		0.501700	Disordered	0.453164	Uncertain	0.332	0.826	0.375											-5.343	Likely Benign	0.495	Ambiguous	Likely Benign										0.135	Likely Benign	-1.10	Neutral	0.872	Possibly Damaging	0.113	Benign	4.00	Benign	0.00	Affected			0.1910	0.4238		0	-1	6.4	-24.99
c.2563C>T	L855F 2D AIThe SynGAP1 missense variant L855F is predicted to be benign by all evaluated in‑silico tools. Consensus predictions from **SGM‑Consensus** (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classify the variant as *Likely Benign*. High‑accuracy predictors **AlphaMissense‑Optimized** also report a benign effect. Other pathogenicity predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default—uniformly predict benign. No tools predict pathogenicity. **Foldetta**, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its stability impact remains unknown. The variant is not listed in ClinVar and has no entry in gnomAD, so no population frequency or clinical annotation is available. Based on the unanimous benign predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-4.985	Likely Benign	0.106	Likely Benign	Likely Benign										0.091	Likely Benign	-1.86	Neutral	0.411	Benign	0.187	Benign	4.00	Benign	0.12	Tolerated			0.0700	0.3529		2	0	-1.0	34.02
c.2564T>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.2575A>C	S859R 2D AIThe SynGAP1 missense variant S859R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized is uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign (two benign versus one pathogenic vote). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.810	In-Between	0.844	Likely Pathogenic	Ambiguous										0.127	Likely Benign	-1.42	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.00	Benign	0.06	Tolerated			0.0945	0.4061		0	-1	-3.7	69.11
c.2575A>G	S859G 2D AIThe SynGAP1 missense variant S859G is not reported in ClinVar and is absent from gnomAD. In silico predictions cluster into three groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized), pathogenic (polyPhen‑2 HumDiv and HumVar), and uncertain (ESM1b). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S859G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.412	In-Between	0.087	Likely Benign	Likely Benign										0.118	Likely Benign	-0.69	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.00	Benign	0.25	Tolerated			0.2798	0.4988		1	0	0.4	-30.03
c.2577T>A	S859R 2D AIThe SynGAP1 missense variant S859R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.810	In-Between	0.844	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.42	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.00	Benign	0.06	Tolerated			0.0945	0.4061		0	-1	-3.7	69.11