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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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.2902G>T | G968C 2D  AIThe SynGAP1 missense variant G968C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.978316 | Disordered | 0.961360 | Binding | 0.327 | 0.896 | 0.750 | -8.441 | Likely Pathogenic | 0.117 | Likely Benign | Likely Benign | 0.170 | Likely Benign | -0.99 | Neutral | 0.992 | Probably Damaging | 0.820 | Possibly Damaging | 4.12 | Benign | 0.07 | Tolerated | 0.1294 | 0.4768 | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||||||
| c.2903G>A | G968D 2D  AIThe SynGAP1 missense variant G968D is catalogued in gnomAD (ID 6‑33443455‑G‑A) but has no ClinVar entry. Across a broad panel of in‑silico predictors, every tool reports a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, so the pathogenic‑prediction group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available for this variant. Consequently, 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 | 0.978316 | Disordered | 0.961360 | Binding | 0.327 | 0.896 | 0.750 | 6-33443455-G-A | 1 | 6.20e-7 | -5.134 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.157 | Likely Benign | -0.48 | Neutral | 0.440 | Benign | 0.198 | Benign | 4.19 | Benign | 0.21 | Tolerated | 4.32 | 2 | 0.1965 | 0.3243 | -1 | 1 | -3.1 | 58.04 | ||||||||||||||||||||||||||||||||||
| c.2903G>C | G968A 2D  AIThe SynGAP1 missense variant G968A is predicted to be benign by all available in‑silico tools. Consensus predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign. No tools predict pathogenicity, so the pathogenic group is empty. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus indicates “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the unanimous benign predictions and the absence of ClinVar evidence, the variant is most likely benign and does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.978316 | Disordered | 0.961360 | Binding | 0.327 | 0.896 | 0.750 | -4.721 | Likely Benign | 0.070 | Likely Benign | Likely Benign | 0.076 | Likely Benign | -0.33 | Neutral | 0.245 | Benign | 0.140 | Benign | 4.24 | Benign | 0.68 | Tolerated | 0.3401 | 0.5154 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2903G>T | G968V 2D  AIThe SynGAP1 missense variant G968V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.978316 | Disordered | 0.961360 | Binding | 0.327 | 0.896 | 0.750 | -6.152 | Likely Benign | 0.093 | Likely Benign | Likely Benign | 0.239 | Likely Benign | -1.08 | Neutral | 0.918 | Possibly Damaging | 0.525 | Possibly Damaging | 4.19 | Benign | 0.11 | Tolerated | 0.1252 | 0.4036 | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||||||
| c.3304G>A | A1102T 2D  AIThe SynGAP1 missense variant A1102T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443856‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 effect, and this does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | Uncertain | 1 | 6-33443856-G-A | 11 | 7.17e-6 | -3.540 | Likely Benign | 0.070 | Likely Benign | Likely Benign | 0.044 | Likely Benign | -0.30 | Neutral | 0.001 | Benign | 0.001 | Benign | 2.32 | Pathogenic | 0.95 | Tolerated | 3.77 | 5 | 0.1755 | 0.7699 | 1 | 0 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||||
| c.3304G>C | A1102P 2D  AIThe SynGAP1 missense variant A1102P is listed in ClinVar (ID 2789225.0) 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), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | Uncertain | 1 | -5.120 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.118 | Likely Benign | -0.97 | Neutral | 0.000 | Benign | 0.002 | Benign | 2.26 | Pathogenic | 0.13 | Tolerated | 3.77 | 5 | 0.1978 | 0.5919 | -1 | 1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.3304G>T | A1102S 2D  AIThe SynGAP1 missense variant A1102S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict 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 | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | -2.900 | Likely Benign | 0.067 | Likely Benign | Likely Benign | 0.041 | Likely Benign | 0.05 | Neutral | 0.019 | Benign | 0.032 | Benign | 2.57 | Benign | 0.59 | Tolerated | 0.2666 | 0.6501 | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3305C>A | A1102D 2D  AIThe SynGAP1 missense variant A1102D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | -4.647 | Likely Benign | 0.388 | Ambiguous | Likely Benign | 0.081 | Likely Benign | -1.38 | Neutral | 0.033 | Benign | 0.028 | Benign | 2.27 | Pathogenic | 0.12 | Tolerated | 0.2045 | 0.2984 | 0 | -2 | -5.3 | 44.01 | ||||||||||||||||||||||||||||||||||||||||
| c.3305C>G | A1102G 2D  AIThe SynGAP1 A1102G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM 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 that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | -3.070 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.39 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.30 | Pathogenic | 0.14 | Tolerated | 0.1947 | 0.4958 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3305C>T | A1102V 2D  AIThe SynGAP1 missense variant A1102V is listed in ClinVar (ID 2846719.0) as Benign and is present in gnomAD (variant ID 6‑33443857‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.915074 | Disordered | 0.962659 | Binding | 0.388 | 0.859 | 0.875 | Benign | 1 | 6-33443857-C-T | -2.440 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.081 | Likely Benign | -1.27 | Neutral | 0.017 | Benign | 0.028 | Benign | 2.29 | Pathogenic | 0.12 | Tolerated | 3.77 | 5 | 0.1333 | 0.6264 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||
| c.2809G>A | D937N 2D  AIThe SynGAP1 missense variant D937N 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 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further corroborate this view: AlphaMissense‑Optimized indicates benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact for D937N, 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 | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -4.259 | Likely Benign | 0.348 | Ambiguous | Likely Benign | 0.095 | Likely Benign | -0.22 | Neutral | 0.561 | Possibly Damaging | 0.139 | Benign | 2.72 | Benign | 0.81 | Tolerated | 0.2430 | 0.7825 | 2 | 1 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||||||
| c.2809G>C | D937H 2D  AIThe SynGAP1 D937H missense variant (ClinVar ID 2825773.0) is listed as “Uncertain” and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote) is benign, and Foldetta (protein‑folding stability analysis combining FoldX‑MD and Rosetta) data are unavailable. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, which is consistent with its ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | Uncertain | 1 | -0.733 | Likely Benign | 0.677 | Likely Pathogenic | Likely Benign | 0.150 | Likely Benign | -1.74 | Neutral | 1.000 | Probably Damaging | 0.975 | Probably Damaging | 2.68 | Benign | 0.13 | Tolerated | 3.77 | 5 | 0.2792 | 0.8228 | -1 | 1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||
| c.2809G>T | D937Y 2D  AIThe SynGAP1 missense variant D937Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic based on current computational evidence, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -4.720 | Likely Benign | 0.711 | Likely Pathogenic | Likely Benign | 0.137 | Likely Benign | -2.52 | Deleterious | 1.000 | Probably Damaging | 0.983 | Probably Damaging | 2.67 | Benign | 0.05 | Affected | 0.1305 | 0.7494 | -4 | -3 | 2.2 | 48.09 | ||||||||||||||||||||||||||||||||||||||||
| c.2810A>C | D937A 2D  AIThe SynGAP1 missense variant D937A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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 classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -1.652 | Likely Benign | 0.385 | Ambiguous | Likely Benign | 0.096 | Likely Benign | -1.45 | Neutral | 0.995 | Probably Damaging | 0.895 | Possibly Damaging | 2.76 | Benign | 0.10 | Tolerated | 0.4296 | 0.7244 | 0 | -2 | 5.3 | -44.01 | |||||||||||||||||||||||||||||||||||||||
| c.2810A>G | D937G 2D  AIThe SynGAP1 missense variant D937G is not reported 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 prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that D937G 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 | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -0.770 | Likely Benign | 0.301 | Likely Benign | Likely Benign | 0.155 | Likely Benign | -0.93 | Neutral | 0.990 | Probably Damaging | 0.817 | Possibly Damaging | 2.82 | Benign | 0.72 | Tolerated | 0.4313 | 0.7006 | 1 | -1 | 3.1 | -58.04 | |||||||||||||||||||||||||||||||||||||||
| c.2810A>T | D937V 2D  AIThe SynGAP1 missense variant D937V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the D937V variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -3.418 | Likely Benign | 0.673 | Likely Pathogenic | Likely Benign | 0.141 | Likely Benign | -2.21 | Neutral | 1.000 | Probably Damaging | 0.977 | Probably Damaging | 2.70 | Benign | 0.02 | Affected | 0.1766 | 0.7408 | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||||||
| c.2811T>A | D937E 2D  AIThe SynGAP1 missense variant D937E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -3.342 | Likely Benign | 0.216 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -1.07 | Neutral | 0.990 | Probably Damaging | 0.801 | Possibly Damaging | 2.76 | Benign | 0.15 | Tolerated | 0.2524 | 0.6915 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2811T>G | D937E 2D AIThe SynGAP1 D937E 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, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the preponderance of benign predictions and the consensus from high‑accuracy methods, 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 | 0.819762 | Disordered | 0.963385 | Binding | 0.348 | 0.883 | 0.625 | -3.342 | Likely Benign | 0.216 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -1.07 | Neutral | 0.990 | Probably Damaging | 0.801 | Possibly Damaging | 2.76 | Benign | 0.15 | Tolerated | 0.2524 | 0.6915 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2920G>A | D974N 2D AIThe SynGAP1 missense variant D974N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect. Consensus predictors such as SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and high‑accuracy methods including AlphaMissense‑Optimized all classify the variant as benign. Additional in silico assessments—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—also predict a benign outcome. No tool in the dataset suggests pathogenicity. Protein‑stability analysis via Foldetta is unavailable for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -4.051 | Likely Benign | 0.145 | Likely Benign | Likely Benign | 0.088 | Likely Benign | -0.35 | Neutral | 0.144 | Benign | 0.085 | Benign | 4.20 | Benign | 0.09 | Tolerated | 0.1972 | 0.7698 | 2 | 1 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||||||
| c.2920G>C | D974H 2D AIThe SynGAP1 missense variant D974H is not reported 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 | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -3.034 | Likely Benign | 0.333 | Likely Benign | Likely Benign | 0.109 | Likely Benign | -0.95 | Neutral | 0.744 | Possibly Damaging | 0.382 | Benign | 4.14 | Benign | 0.02 | Affected | 0.2249 | 0.7803 | 1 | -1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2920G>T | D974Y 2D AIThe SynGAP1 missense variant D974Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of computational evidence points to a benign impact, which is consistent with the absence of ClinVar pathogenic classification and gnomAD observations. Thus, the variant is most likely benign, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -4.290 | Likely Benign | 0.384 | Ambiguous | Likely Benign | 0.130 | Likely Benign | -1.85 | Neutral | 0.716 | Possibly Damaging | 0.284 | Benign | 4.13 | Benign | 0.01 | Affected | 0.1072 | 0.6627 | -4 | -3 | 2.2 | 48.09 | |||||||||||||||||||||||||||||||||||||||
| c.2921A>C | D974A 2D AIThe SynGAP1 missense variant D974A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that D974A 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 | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -2.619 | Likely Benign | 0.224 | Likely Benign | Likely Benign | 0.242 | Likely Benign | -0.96 | Neutral | 0.001 | Benign | 0.002 | Benign | 4.22 | Benign | 0.04 | Affected | 0.3398 | 0.7129 | 0 | -2 | 5.3 | -44.01 | |||||||||||||||||||||||||||||||||||||||
| c.2921A>G | D974G 2D AIThe SynGAP1 missense variant D974G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -1.638 | Likely Benign | 0.188 | Likely Benign | Likely Benign | 0.203 | Likely Benign | -0.72 | Neutral | 0.036 | Benign | 0.026 | Benign | 4.18 | Benign | 0.06 | Tolerated | 0.3379 | 0.6771 | 1 | -1 | 3.1 | -58.04 | |||||||||||||||||||||||||||||||||||||||
| c.2921A>T | D974V 2D AIThe SynGAP1 missense variant D974V is not reported 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, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective predictions strongly suggest that D974V 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 | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -3.629 | Likely Benign | 0.351 | Ambiguous | Likely Benign | 0.211 | Likely Benign | -1.49 | Neutral | 0.001 | Benign | 0.002 | Benign | 4.16 | Benign | 0.01 | Affected | 0.1449 | 0.7286 | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||||||
| c.2922C>A | D974E 2D AIThe SynGAP1 missense variant D974E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -3.617 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.078 | Likely Benign | -0.63 | Neutral | 0.036 | Benign | 0.026 | Benign | 4.26 | Benign | 0.05 | Affected | 0.2119 | 0.7516 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2922C>G | D974E 2D AIThe SynGAP1 missense variant D974E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.964377 | Binding | 0.389 | 0.897 | 0.625 | -3.617 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.078 | Likely Benign | -0.63 | Neutral | 0.036 | Benign | 0.026 | Benign | 4.26 | Benign | 0.05 | Affected | 0.2119 | 0.7516 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2767A>C | I923L 2D  AIThe SynGAP1 missense variant I923L is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors—including REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | -1.637 | Likely Benign | 0.157 | Likely Benign | Likely Benign | 0.069 | Likely Benign | -0.03 | Neutral | 0.166 | Benign | 0.101 | Benign | 2.82 | Benign | 0.56 | Tolerated | 0.1133 | 0.4528 | 2 | 2 | -0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.2767A>G | I923V 2D  AIThe SynGAP1 missense variant I923V is reported in gnomAD (ID 6‑33443319‑A‑G) and has no ClinVar entry. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this is consistent with the absence of a ClinVar pathogenic classification. Therefore, the variant is most likely benign, with no conflict with ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | 6-33443319-A-G | 1 | 6.20e-7 | -2.010 | Likely Benign | 0.113 | Likely Benign | Likely Benign | 0.059 | Likely Benign | 0.05 | Neutral | 0.028 | Benign | 0.009 | Benign | 2.76 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0.1589 | 0.4060 | 3 | 4 | -0.3 | -14.03 | ||||||||||||||||||||||||||||||||||
| c.2767A>T | I923F 2D  AIThe SynGAP1 missense variant I923F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | -2.967 | Likely Benign | 0.169 | Likely Benign | Likely Benign | 0.112 | Likely Benign | -0.85 | Neutral | 0.007 | Benign | 0.005 | Benign | 2.70 | Benign | 0.11 | Tolerated | 0.0726 | 0.3887 | 1 | 0 | -1.7 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2768T>A | I923N 2D  AIThe SynGAP1 missense variant I923N (ClinVar ID 647043.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign” because the majority of its constituent tools (three benign, one pathogenic) favor a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the collective predictions point to a benign impact, which does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | Uncertain | 1 | -0.733 | Likely Benign | 0.712 | Likely Pathogenic | Likely Benign | 0.108 | Likely Benign | -1.16 | Neutral | 0.991 | Probably Damaging | 0.793 | Possibly Damaging | 2.70 | Benign | 0.13 | Tolerated | 3.77 | 5 | 0.1164 | 0.1073 | -2 | -3 | -8.0 | 0.94 | |||||||||||||||||||||||||||||||||||
| c.2768T>C | I923T 2D  AIThe SynGAP1 missense variant I923T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 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 | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | -1.180 | Likely Benign | 0.842 | Likely Pathogenic | Ambiguous | 0.097 | Likely Benign | -0.53 | Neutral | 0.837 | Possibly Damaging | 0.348 | Benign | 2.73 | Benign | 0.41 | Tolerated | 0.1327 | 0.1786 | 0 | -1 | -5.2 | -12.05 | |||||||||||||||||||||||||||||||||||||||
| c.2768T>G | I923S 2D  AIThe SynGAP1 missense variant I923S is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for I923S. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | -0.002 | Likely Benign | 0.760 | Likely Pathogenic | Likely Benign | 0.094 | Likely Benign | -0.61 | Neutral | 0.912 | Possibly Damaging | 0.529 | Possibly Damaging | 2.73 | Benign | 0.33 | Tolerated | 0.3300 | 0.1455 | -1 | -2 | -5.3 | -26.08 | |||||||||||||||||||||||||||||||||||||||
| c.2769C>G | I923M 2D  AIThe SynGAP1 missense variant I923M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that I923M 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 | 0.562014 | Disordered | 0.964857 | Binding | 0.292 | 0.852 | 0.250 | -2.711 | Likely Benign | 0.195 | Likely Benign | Likely Benign | 0.106 | Likely Benign | -0.14 | Neutral | 0.973 | Probably Damaging | 0.721 | Possibly Damaging | 2.70 | Benign | 0.16 | Tolerated | 0.0949 | 0.3874 | 2 | 1 | -2.6 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3055C>A | R1019S 2D  AIThe SynGAP1 missense variant R1019S is not 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 ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote) remains Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for R1019S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | -3.818 | Likely Benign | 0.871 | Likely Pathogenic | Ambiguous | 0.113 | Likely Benign | -2.59 | Deleterious | 0.800 | Possibly Damaging | 0.410 | Benign | 2.43 | Pathogenic | 0.01 | Affected | 0.2441 | 0.3979 | 0 | -1 | 3.7 | -69.11 | |||||||||||||||||||||||||||||||||||||||
| c.3055C>G | R1019G 2D  AIThe SynGAP1 missense variant R1019G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas tools predicting a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions support a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | -4.325 | Likely Benign | 0.614 | Likely Pathogenic | Likely Benign | 0.115 | Likely Benign | -3.34 | Deleterious | 0.800 | Possibly Damaging | 0.496 | Possibly Damaging | 2.39 | Pathogenic | 0.00 | Affected | 0.2946 | 0.3489 | -3 | -2 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||||||||||
| c.3055C>T | R1019C 2D  AIThe SynGAP1 missense variant R1019C is listed in ClinVar with an “Uncertain” status (ClinVar ID 1676922.0) and is present in gnomAD (ID 6‑33443607‑C‑T). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote) remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | Conflicting | 2 | 6-33443607-C-T | 10 | 6.19e-6 | -7.386 | In-Between | 0.646 | Likely Pathogenic | Likely Benign | 0.168 | Likely Benign | -4.00 | Deleterious | 0.999 | Probably Damaging | 0.880 | Possibly Damaging | 2.36 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.3016 | 0.3664 | -4 | -3 | 7.0 | -53.05 | 10.1016/j.ajhg.2020.11.011 | |||||||||||||||||||||||||||||||
| c.3056G>A | R1019H 2D  AIThe SynGAP1 missense variant R1019H is listed in ClinVar (ID 1195115.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443608‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact for R1019H, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | Conflicting | 2 | 6-33443608-G-A | 67 | 4.15e-5 | -4.610 | Likely Benign | 0.258 | Likely Benign | Likely Benign | 0.122 | Likely Benign | -1.95 | Neutral | 0.995 | Probably Damaging | 0.845 | Possibly Damaging | 2.39 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.2400 | 0.1903 | 2 | 0 | 1.3 | -19.05 | ||||||||||||||||||||||||||||||||
| c.3056G>C | R1019P 2D  AIThe SynGAP1 missense variant R1019P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, whereas those that predict pathogenicity are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of conventional tools predict a pathogenic effect, but the most accurate single‑tool prediction is benign and the consensus and folding‑stability analyses are inconclusive. Thus, the variant is most likely pathogenic based on the aggregate 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. | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | -3.737 | Likely Benign | 0.697 | Likely Pathogenic | Likely Benign | 0.143 | Likely Benign | -2.48 | Neutral | 0.966 | Probably Damaging | 0.811 | Possibly Damaging | 2.38 | Pathogenic | 0.01 | Affected | 0.1899 | 0.4521 | 0 | -2 | 2.9 | -59.07 | ||||||||||||||||||||||||||||||||||||||||
| c.3056G>T | R1019L 2D  AIThe SynGAP1 missense variant R1019L is listed in ClinVar with an “Uncertain” status (ClinVar ID 3364537.0) and is present in gnomAD (gnomAD ID 6‑33443608‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, 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 majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.856457 | Disordered | 0.966400 | Binding | 0.315 | 0.794 | 0.500 | Uncertain | 1 | 6-33443608-G-T | 2 | 1.24e-6 | -5.194 | Likely Benign | 0.752 | Likely Pathogenic | Likely Benign | 0.110 | Likely Benign | -3.57 | Deleterious | 0.800 | Possibly Damaging | 0.573 | Possibly Damaging | 2.40 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.1850 | 0.4886 | -2 | -3 | 8.3 | -43.03 | ||||||||||||||||||||||||||||||||
| 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.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.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>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.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.2945A>T | Y982F 2D  AIThe SynGAP1 missense variant Y982F is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.966717 | Binding | 0.272 | 0.895 | 0.625 | -3.431 | Likely Benign | 0.208 | Likely Benign | Likely Benign | 0.154 | Likely Benign | -0.36 | Neutral | 0.006 | Benign | 0.009 | Benign | 4.63 | Benign | 0.00 | Affected | 0.2351 | 0.2980 | 7 | 3 | 4.1 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3121C>A | P1041T 2D  AIThe SynGAP1 missense variant P1041T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar annotation (none present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | -5.009 | Likely Benign | 0.187 | Likely Benign | Likely Benign | 0.361 | Likely Benign | -2.45 | Neutral | 0.051 | Benign | 0.025 | Benign | 5.50 | Benign | 0.10 | Tolerated | 0.1632 | 0.6699 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3121C>G | P1041A 2D  AIThe SynGAP1 missense variant P1041A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. 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. 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 | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | -4.597 | Likely Benign | 0.157 | Likely Benign | Likely Benign | 0.331 | Likely Benign | -2.73 | Deleterious | 0.798 | Possibly Damaging | 0.283 | Benign | 5.53 | Benign | 0.24 | Tolerated | 0.3154 | 0.5939 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3121C>T | P1041S 2D  AIThe SynGAP1 missense variant P1041S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443673‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | Conflicting | 2 | 6-33443673-C-T | 1 | 6.20e-7 | -4.246 | Likely Benign | 0.121 | Likely Benign | Likely Benign | 0.344 | Likely Benign | -2.72 | Deleterious | 0.664 | Possibly Damaging | 0.283 | Benign | 5.48 | Benign | 0.11 | Tolerated | 3.77 | 5 | 0.3199 | 0.6120 | 1 | -1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||||
| c.3122C>A | P1041H 2D  AIThe SynGAP1 missense variant P1041H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, and Foldetta’s protein‑folding stability result is unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status because the variant has not been reported there. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | -5.312 | Likely Benign | 0.377 | Ambiguous | Likely Benign | 0.476 | Likely Benign | -3.32 | Deleterious | 0.999 | Probably Damaging | 0.917 | Probably Damaging | 5.45 | Benign | 0.03 | Affected | 0.1883 | 0.5434 | 0 | -2 | -1.6 | 40.02 | ||||||||||||||||||||||||||||||||||||||||
| c.3122C>G | P1041R 2D  AIThe SynGAP1 missense variant P1041R 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, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The AlphaMissense‑Default result is uncertain, and no Foldetta stability data are available, so these are treated as unavailable. Overall, six tools support a benign classification while three support pathogenicity, and the high‑accuracy AlphaMissense‑Optimized and SGM Consensus both predict benign. Therefore, the variant is most likely benign based on the current predictions, 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. | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | -4.808 | Likely Benign | 0.545 | Ambiguous | Likely Benign | 0.443 | Likely Benign | -3.33 | Deleterious | 0.986 | Probably Damaging | 0.787 | Possibly Damaging | 5.46 | Benign | 0.07 | Tolerated | 0.1401 | 0.4292 | 0 | -2 | -2.9 | 59.07 | ||||||||||||||||||||||||||||||||||||||||
| c.3122C>T | P1041L 2D  AIThe SynGAP1 missense variant P1041L 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign. 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 ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.962114 | Disordered | 0.967463 | Binding | 0.345 | 0.833 | 0.625 | -4.901 | Likely Benign | 0.399 | Ambiguous | Likely Benign | 0.403 | Likely Benign | -3.14 | Deleterious | 0.905 | Possibly Damaging | 0.375 | Benign | 5.46 | Benign | 1.00 | Tolerated | 0.2357 | 0.6664 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||||||
| c.4003G>A | G1335S 2D  AIThe SynGAP1 missense variant G1335S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33451877‑G‑A). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, 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, PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that G1335S is most likely pathogenic, 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 | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | Conflicting | 2 | 6-33451877-G-A | 3 | 2.37e-6 | -4.495 | Likely Benign | 0.986 | Likely Pathogenic | Likely Pathogenic | 0.362 | Likely Benign | -3.79 | Deleterious | 1.000 | Probably Damaging | 0.997 | Probably Damaging | 2.04 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.2452 | 0.5895 | 1 | 0 | -0.4 | 30.03 | ||||||||||||||||||||||||||||||||
| c.4003G>C | G1335R 2D  AIThe SynGAP1 missense variant G1335R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available. Overall, the preponderance of evidence supports a pathogenic classification for G1335R, 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 | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | -4.921 | Likely Benign | 0.997 | Likely Pathogenic | Likely Pathogenic | 0.394 | Likely Benign | -5.06 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.02 | Pathogenic | 0.00 | Affected | 0.1071 | 0.5024 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||||||
| c.4003G>T | G1335C 2D AIThe SynGAP1 missense variant G1335C is listed in gnomAD (variant ID 6-33451877‑G‑T) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | 6-33451877-G-T | 1 | 7.91e-7 | -6.878 | Likely Benign | 0.997 | Likely Pathogenic | Likely Pathogenic | 0.426 | Likely Benign | -5.51 | Deleterious | 1.000 | Probably Damaging | 1.000 | Probably Damaging | 2.01 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.1376 | 0.4513 | -3 | -3 | 2.9 | 46.09 | ||||||||||||||||||||||||||||||||||
| c.4004G>A | G1335D 2D AIThe SynGAP1 missense variant G1335D is reported in ClinVar as “not listed” and is present in gnomAD (variant ID 6‑33451878‑G‑A). Functional prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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 impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) 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 G1335D 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 | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | 6-33451878-G-A | -5.687 | Likely Benign | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.404 | Likely Benign | -4.42 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.02 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.2120 | 0.3702 | -1 | 1 | -3.1 | 58.04 | ||||||||||||||||||||||||||||||||||||
| c.4004G>C | G1335A 2D AIThe SynGAP1 missense variant G1335A is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for G1335A, 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 | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | -4.942 | Likely Benign | 0.993 | Likely Pathogenic | Likely Pathogenic | 0.357 | Likely Benign | -3.69 | Deleterious | 0.996 | Probably Damaging | 0.992 | Probably Damaging | 2.05 | Pathogenic | 0.00 | Affected | 0.3383 | 0.4953 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.4004G>T | G1335V 2D AIThe SynGAP1 missense variant G1335V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for G1335V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.891961 | Disordered | 0.967705 | Binding | 0.323 | 0.724 | 0.750 | -4.982 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.394 | Likely Benign | -5.65 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.02 | Pathogenic | 0.00 | Affected | 0.1124 | 0.4195 | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||||||
| c.3931C>A | L1311M 2D  AIThe SynGAP1 missense variant L1311M is reported in gnomAD (ID 6‑33451805‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates “Likely Benign.” In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign classification for L1311M, 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 | 0.816150 | Disordered | 0.968153 | Binding | 0.393 | 0.907 | 0.750 | 6-33451805-C-A | 3 | 1.86e-6 | -4.817 | Likely Benign | 0.099 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.18 | Neutral | 0.936 | Possibly Damaging | 0.632 | Possibly Damaging | 2.73 | Benign | 0.23 | Tolerated | 3.77 | 5 | 0.1068 | 0.4279 | 2 | 4 | -1.9 | 18.03 | ||||||||||||||||||||||||||||||||||
| c.3931C>G | L1311V 2D  AIThe SynGAP1 missense variant L1311V is catalogued in gnomAD (ID 6‑33451805‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.968153 | Binding | 0.393 | 0.907 | 0.750 | 6-33451805-C-G | 1 | 6.20e-7 | -3.645 | Likely Benign | 0.066 | Likely Benign | Likely Benign | 0.025 | Likely Benign | -0.05 | Neutral | 0.362 | Benign | 0.193 | Benign | 2.89 | Benign | 0.32 | Tolerated | 3.77 | 5 | 0.1666 | 0.3518 | 1 | 2 | 0.4 | -14.03 | ||||||||||||||||||||||||||||||||||
| c.3932T>A | L1311Q 2D  AIThe SynGAP1 missense variant L1311Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence 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 | 0.816150 | Disordered | 0.968153 | Binding | 0.393 | 0.907 | 0.750 | -4.009 | Likely Benign | 0.100 | Likely Benign | Likely Benign | 0.074 | Likely Benign | -0.03 | Neutral | 0.579 | Possibly Damaging | 0.413 | Benign | 2.74 | Benign | 0.12 | Tolerated | 0.1476 | 0.1677 | -2 | -2 | -7.3 | 14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3932T>C | L1311P 2D  AIThe SynGAP1 missense variant L1311P is listed in ClinVar (ID 833866.0) as Benign and is present in gnomAD (variant ID 6‑33451806‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized also reports Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of computational evidence supports a benign effect, which is consistent with the ClinVar benign annotation and does not contradict the database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.968153 | Binding | 0.393 | 0.907 | 0.750 | Likely Benign | 1 | 6-33451806-T-C | 1 | 6.21e-7 | -1.831 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.123 | Likely Benign | -0.52 | Neutral | 0.579 | Possibly Damaging | 0.335 | Benign | 2.72 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.3181 | 0.1794 | -3 | -3 | -5.4 | -16.04 | ||||||||||||||||||||||||||||||||
| c.3932T>G | L1311R 2D  AIThe SynGAP1 missense variant L1311R is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the change as tolerated or benign. Only polyPhen‑2 HumDiv classifies it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy tools further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the evidence overwhelmingly points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.968153 | Binding | 0.393 | 0.907 | 0.750 | -3.794 | Likely Benign | 0.169 | Likely Benign | Likely Benign | 0.083 | Likely Benign | -0.36 | Neutral | 0.579 | Possibly Damaging | 0.267 | Benign | 2.74 | Benign | 0.12 | Tolerated | 0.1611 | 0.1719 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.3952C>A | L1318M 2D AIThe SynGAP1 missense variant L1318M is listed in gnomAD (ID 6‑33451826‑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, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.968271 | Binding | 0.399 | 0.865 | 0.750 | 6-33451826-C-A | -4.625 | Likely Benign | 0.117 | Likely Benign | Likely Benign | 0.039 | Likely Benign | -0.62 | Neutral | 0.939 | Possibly Damaging | 0.396 | Benign | 4.01 | Benign | 0.03 | Affected | 3.77 | 5 | 0.1083 | 0.4027 | 2 | 4 | -1.9 | 18.03 | ||||||||||||||||||||||||||||||||||||
| c.3952C>G | L1318V 2D AIThe SynGAP1 missense variant L1318V is catalogued in gnomAD (ID 6‑33451826‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar record, which contains no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.968271 | Binding | 0.399 | 0.865 | 0.750 | 6-33451826-C-G | 1 | 6.31e-7 | -3.938 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.038 | Likely Benign | -0.58 | Neutral | 0.113 | Benign | 0.028 | Benign | 4.08 | Benign | 0.75 | Tolerated | 3.77 | 5 | 0.1861 | 0.3027 | 1 | 2 | 0.4 | -14.03 | ||||||||||||||||||||||||||||||||||
| c.3953T>A | L1318Q 2D AIThe SynGAP1 missense variant L1318Q is reported in gnomAD (variant ID 6‑33451827‑T‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, 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. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.968271 | Binding | 0.399 | 0.865 | 0.750 | 6-33451827-T-A | 1 | 6.32e-7 | -3.445 | Likely Benign | 0.120 | Likely Benign | Likely Benign | 0.077 | Likely Benign | -2.06 | Neutral | 0.834 | Possibly Damaging | 0.307 | Benign | 4.04 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1410 | 0.0903 | -2 | -2 | -7.3 | 14.97 | ||||||||||||||||||||||||||||||||||
| 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.3953T>G | L1318R 2D AIThe SynGAP1 missense variant L1318R is reported in gnomAD (variant ID 6-33451827‑T‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign effect, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.968271 | Binding | 0.399 | 0.865 | 0.750 | 6-33451827-T-G | -3.381 | Likely Benign | 0.187 | Likely Benign | Likely Benign | 0.081 | Likely Benign | -1.58 | Neutral | 0.588 | Possibly Damaging | 0.212 | Benign | 4.01 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1429 | 0.1303 | -2 | -3 | -8.3 | 43.03 | ||||||||||||||||||||||||||||||||||||
| c.3196C>A | P1066T 2D AIThe SynGAP1 missense variant P1066T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | -5.973 | Likely Benign | 0.082 | Likely Benign | Likely Benign | 0.167 | Likely Benign | -2.61 | Deleterious | 0.996 | Probably Damaging | 0.928 | Probably Damaging | 2.66 | Benign | 0.00 | Affected | 0.1652 | 0.7240 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3196C>G | P1066A 2D AIThe SynGAP1 missense variant P1066A 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 | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | -4.856 | Likely Benign | 0.050 | Likely Benign | Likely Benign | 0.149 | Likely Benign | -2.35 | Neutral | 0.972 | Probably Damaging | 0.802 | Possibly Damaging | 2.78 | Benign | 0.00 | Affected | 0.3228 | 0.6042 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3196C>T | P1066S 2D AIThe SynGAP1 missense variant P1066S is listed in ClinVar as Pathogenic (ClinVar ID 1343237.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, which contradicts the ClinVar pathogenic classification. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | Likely Pathogenic | 1 | -4.746 | Likely Benign | 0.070 | Likely Benign | Likely Benign | 0.145 | Likely Benign | -2.47 | Neutral | 0.972 | Probably Damaging | 0.850 | Possibly Damaging | 2.74 | Benign | 0.00 | Affected | 4.32 | 2 | 0.3304 | 0.6353 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||
| c.3197C>A | P1066H 2D AIThe SynGAP1 missense variant P1066H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | -6.034 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.146 | Likely Benign | -2.90 | Deleterious | 1.000 | Probably Damaging | 0.975 | Probably Damaging | 2.61 | Benign | 0.00 | Affected | 0.1984 | 0.5861 | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||||||
| c.3197C>G | P1066R 2D AIThe SynGAP1 missense variant P1066R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. 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 computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | -5.154 | Likely Benign | 0.292 | Likely Benign | Likely Benign | 0.176 | Likely Benign | -2.89 | Deleterious | 0.992 | Probably Damaging | 0.873 | Possibly Damaging | 2.63 | Benign | 0.00 | Affected | 0.1523 | 0.4742 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3197C>T | P1066L 2D AIThe SynGAP1 missense variant P1066L is listed in ClinVar as a benign variant (ClinVar ID 951518.0) and is present in gnomAD (ID 6‑33443749‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are 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, 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. | Likely Benign | 0.967676 | Disordered | 0.968838 | Binding | 0.403 | 0.913 | 0.875 | Likely Benign | 1 | 6-33443749-C-T | 14 | 8.71e-6 | -5.478 | Likely Benign | 0.092 | Likely Benign | Likely Benign | 0.173 | Likely Benign | -3.68 | Deleterious | 0.996 | Probably Damaging | 0.903 | Possibly Damaging | 2.72 | Benign | 0.00 | Affected | 4.32 | 2 | 0.2269 | 0.6780 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||
| c.2869C>A | H957N 2D  AIThe SynGAP1 missense variant H957N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only FATHMM predicts a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. 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 | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -6.804 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.053 | Likely Benign | -0.45 | Neutral | 0.144 | Benign | 0.058 | Benign | 2.45 | Pathogenic | 0.50 | Tolerated | 0.2343 | 0.3788 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2869C>G | H957D 2D  AIThe SynGAP1 missense variant H957D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (7 benign vs 2 pathogenic) supports a benign classification. This prediction is consistent with the lack of ClinVar annotation and gnomAD presence, indicating no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -8.777 | Likely Pathogenic | 0.237 | Likely Benign | Likely Benign | 0.149 | Likely Benign | -0.77 | Neutral | 0.144 | Benign | 0.058 | Benign | 2.45 | Pathogenic | 0.44 | Tolerated | 0.2646 | 0.3066 | 1 | -1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||||||||||||
| c.2869C>T | H957Y 2D  AIThe SynGAP1 missense variant H957Y is listed in gnomAD (ID 6‑33443421‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which reports “Likely Benign.” Pathogenic predictions come from polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as 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 | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | 6-33443421-C-T | 1 | 6.20e-7 | -6.631 | Likely Benign | 0.129 | Likely Benign | Likely Benign | 0.099 | Likely Benign | -1.00 | Neutral | 0.510 | Possibly Damaging | 0.147 | Benign | 2.42 | Pathogenic | 0.10 | Tolerated | 3.77 | 5 | 0.1560 | 0.4906 | 2 | 0 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||
| c.2870A>C | H957P 2D  AIThe SynGAP1 H957P 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, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding 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 status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -6.347 | Likely Benign | 0.061 | Likely Benign | Likely Benign | 0.244 | Likely Benign | -0.61 | Neutral | 0.453 | Possibly Damaging | 0.105 | Benign | 2.42 | Pathogenic | 0.13 | Tolerated | 0.2300 | 0.4701 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2870A>G | H957R 2D  AIThe SynGAP1 missense variant H957R is catalogued in gnomAD (ID 6‑33443422‑A‑G) but has no ClinVar entry. Functional prediction tools uniformly classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes. No tool predicts pathogenicity. Grouping by consensus, all listed predictors fall into the benign category, with no opposing pathogenic calls. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable, so they do not influence the assessment. Overall, the evidence strongly supports a benign classification for H957R, 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 | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | 6-33443422-A-G | 1 | 6.20e-7 | -6.723 | Likely Benign | 0.183 | Likely Benign | Likely Benign | 0.105 | Likely Benign | -1.31 | Neutral | 0.144 | Benign | 0.078 | Benign | 2.58 | Benign | 0.32 | Tolerated | 3.77 | 5 | 0.2410 | 0.3610 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||||
| c.2870A>T | H957L 2D  AIThe SynGAP1 missense variant H957L is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. When predictions are grouped by consensus, the benign group contains eight tools, whereas the pathogenic group contains only FATHMM. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign result. Foldetta, a protein‑folding stability method, has no available output for this variant. Overall, the preponderance of evidence indicates that H957L 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 | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -6.598 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.296 | Likely Benign | -0.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 2.44 | Pathogenic | 0.09 | Tolerated | 0.1525 | 0.5516 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2871T>A | H957Q 2D  AIThe SynGAP1 missense variant H957Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -6.304 | Likely Benign | 0.130 | Likely Benign | Likely Benign | 0.113 | Likely Benign | -0.87 | Neutral | 0.255 | Benign | 0.105 | Benign | 2.54 | Benign | 0.56 | Tolerated | 0.2227 | 0.4114 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2871T>G | H957Q 2D AIThe SynGAP1 missense variant H957Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.968874 | Binding | 0.362 | 0.915 | 0.750 | -6.304 | Likely Benign | 0.130 | Likely Benign | Likely Benign | 0.113 | Likely Benign | -0.87 | Neutral | 0.255 | Benign | 0.105 | Benign | 2.54 | Benign | 0.56 | Tolerated | 0.2227 | 0.4114 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3301C>A | P1101T 2D AIThe SynGAP1 missense variant P1101T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | -4.161 | Likely Benign | 0.070 | Likely Benign | Likely Benign | 0.126 | Likely Benign | -1.60 | Neutral | 0.115 | Benign | 0.031 | Benign | 4.22 | Benign | 0.04 | Affected | 0.1729 | 0.5860 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3301C>G | P1101A 2D AIThe SynGAP1 missense variant P1101A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, 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 | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | -3.825 | Likely Benign | 0.057 | Likely Benign | Likely Benign | 0.095 | Likely Benign | -1.34 | Neutral | 0.010 | Benign | 0.010 | Benign | 4.26 | Benign | 0.08 | Tolerated | 0.3154 | 0.5218 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3301C>T | P1101S 2D AIThe SynGAP1 missense variant P1101S is reported in gnomAD (variant ID 6‑33443853‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | 6-33443853-C-T | 1 | 6.52e-7 | -3.845 | Likely Benign | 0.080 | Likely Benign | Likely Benign | 0.075 | Likely Benign | -1.31 | Neutral | 0.626 | Possibly Damaging | 0.255 | Benign | 4.25 | Benign | 0.07 | Tolerated | 3.77 | 5 | 0.3265 | 0.5400 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||||||
| c.3302C>A | P1101H 2D AIThe SynGAP1 missense variant P1101H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect for P1101H, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | -5.370 | Likely Benign | 0.149 | Likely Benign | Likely Benign | 0.167 | Likely Benign | -1.87 | Neutral | 0.996 | Probably Damaging | 0.864 | Possibly Damaging | 4.18 | Benign | 0.02 | Affected | 0.2046 | 0.4597 | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||||||
| c.3302C>G | P1101R 2D AIThe SynGAP1 missense variant P1101R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of evidence points to a benign effect, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | -4.772 | Likely Benign | 0.227 | Likely Benign | Likely Benign | 0.103 | Likely Benign | -1.28 | Neutral | 0.960 | Probably Damaging | 0.761 | Possibly Damaging | 4.27 | Benign | 0.36 | Tolerated | 0.1497 | 0.4644 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3302C>T | P1101L 2D AIThe SynGAP1 missense variant P1101L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for P1101L, 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 | 0.874069 | Disordered | 0.968967 | Binding | 0.457 | 0.861 | 0.875 | -4.335 | Likely Benign | 0.093 | Likely Benign | Likely Benign | 0.109 | Likely Benign | -2.19 | Neutral | 0.770 | Possibly Damaging | 0.255 | Benign | 4.27 | Benign | 0.04 | Affected | 0.2310 | 0.6050 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| c.2923A>C | T975P 2D  AIThe SynGAP1 missense variant T975P has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | -2.181 | Likely Benign | 0.071 | Likely Benign | Likely Benign | 0.286 | Likely Benign | -1.21 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.14 | Benign | 0.06 | Tolerated | 0.2047 | 0.4758 | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||||||
| c.2923A>G | T975A 2D  AIThe SynGAP1 missense change T975A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this 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 | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | -2.866 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.110 | Likely Benign | -0.71 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.19 | Benign | 0.18 | Tolerated | 0.3821 | 0.4275 | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||||||
| c.2923A>T | T975S 2D  AIThe SynGAP1 missense variant T975S is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the predictions strongly suggest that T975S 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 | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | -2.743 | Likely Benign | 0.068 | Likely Benign | Likely Benign | 0.127 | Likely Benign | -0.57 | Neutral | 0.059 | Benign | 0.061 | Benign | 4.16 | Benign | 0.20 | Tolerated | 0.3228 | 0.4366 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2924C>A | T975N 2D  AIThe SynGAP1 missense variant T975N is listed in ClinVar (ID 942242.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443476‑C‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes. Only polyPhen‑2 HumDiv predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | Uncertain | 1 | 6-33443476-C-A | 1 | 6.20e-7 | -4.671 | Likely Benign | 0.089 | Likely Benign | Likely Benign | 0.100 | Likely Benign | -0.58 | Neutral | 0.586 | Possibly Damaging | 0.302 | Benign | 4.13 | Benign | 0.07 | Tolerated | 4.32 | 2 | 0.1379 | 0.4772 | 0 | 0 | -2.8 | 13.00 | ||||||||||||||||||||||||||||||||
| c.2924C>G | T975S 2D AIThe SynGAP1 missense variant T975S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the available predictions strongly suggest that T975S is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | Uncertain | 1 | -2.743 | Likely Benign | 0.068 | Likely Benign | Likely Benign | 0.109 | Likely Benign | -0.57 | Neutral | 0.059 | Benign | 0.061 | Benign | 4.16 | Benign | 0.20 | Tolerated | 0.3228 | 0.4366 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||
| c.2924C>T | T975I 2D  AIThe SynGAP1 missense variant T975I is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33443476‑C‑T). Prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.871313 | Disordered | 0.969331 | Binding | 0.332 | 0.890 | 0.625 | Uncertain | 1 | 6-33443476-C-T | 6 | 3.72e-6 | -3.912 | Likely Benign | 0.164 | Likely Benign | Likely Benign | 0.068 | Likely Benign | -1.66 | Neutral | 0.411 | Benign | 0.239 | Benign | 4.11 | Benign | 0.66 | Tolerated | 4.32 | 2 | 0.1107 | 0.5198 | 0 | -1 | 5.2 | 12.05 | ||||||||||||||||||||||||||||||||
| c.2899C>G | R967G 2D AIThe SynGAP1 missense variant R967G is reported in gnomAD (ID 6‑33443451‑C‑G) and has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Based on the unanimous benign predictions and absence of a ClinVar pathogenic claim, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.974374 | Disordered | 0.969686 | Binding | 0.340 | 0.888 | 0.750 | 6-33443451-C-G | 1 | 6.20e-7 | -2.214 | Likely Benign | 0.098 | Likely Benign | Likely Benign | 0.279 | Likely Benign | -0.93 | Neutral | 0.005 | Benign | 0.007 | Benign | 4.17 | Benign | 0.18 | Tolerated | 4.32 | 2 | 0.3187 | 0.4070 | -2 | -3 | 4.1 | -99.14 | ||||||||||||||||||||||||||||||||||
| c.2900G>A | R967Q 2D  AIThe SynGAP1 missense variant R967Q is listed in ClinVar as Benign (ClinVar ID 536992.0) and is present in gnomAD (6‑33443452‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.974374 | Disordered | 0.969686 | Binding | 0.340 | 0.888 | 0.750 | Benign/Likely benign | 2 | 6-33443452-G-A | 31 | 1.92e-5 | -3.057 | Likely Benign | 0.080 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -0.01 | Neutral | 0.994 | Probably Damaging | 0.626 | Possibly Damaging | 4.21 | Benign | 0.36 | Tolerated | 4.32 | 2 | 0.3141 | 0.3446 | 1 | 1 | 1.0 | -28.06 | ||||||||||||||||||||||||||||||||
| c.2900G>C | R967P 2D AIThe SynGAP1 missense variant R967P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic 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 R967P, 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 | 0.974374 | Disordered | 0.969686 | Binding | 0.340 | 0.888 | 0.750 | -2.506 | Likely Benign | 0.132 | Likely Benign | Likely Benign | 0.175 | Likely Benign | -0.76 | Neutral | 0.996 | Probably Damaging | 0.828 | Possibly Damaging | 4.14 | Benign | 0.17 | Tolerated | 0.2145 | 0.5533 | 0 | -2 | 2.9 | -59.07 | |||||||||||||||||||||||||||||||||||||||
| c.2900G>T | R967L 2D AIThe SynGAP1 missense variant R967L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443452‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R967L, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.974374 | Disordered | 0.969686 | Binding | 0.340 | 0.888 | 0.750 | Uncertain | 1 | 6-33443452-G-T | 1 | 6.20e-7 | -3.496 | Likely Benign | 0.164 | Likely Benign | Likely Benign | 0.123 | Likely Benign | -0.99 | Neutral | 0.959 | Probably Damaging | 0.586 | Possibly Damaging | 4.15 | Benign | 0.75 | Tolerated | 4.32 | 2 | 0.1964 | 0.5093 | -2 | -3 | 8.3 | -43.03 | ||||||||||||||||||||||||||||||||
| c.3937C>A | P1313T 2D AIThe SynGAP1 missense variant P1313T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -4.666 | Likely Benign | 0.071 | Likely Benign | Likely Benign | 0.149 | Likely Benign | 0.03 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.26 | Benign | 0.14 | Tolerated | 0.1889 | 0.7040 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3937C>G | P1313A 2D AIThe SynGAP1 missense variant P1313A is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this benign classification: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that P1313A 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 | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -3.855 | Likely Benign | 0.054 | Likely Benign | Likely Benign | 0.069 | Likely Benign | -0.37 | Neutral | 0.021 | Benign | 0.028 | Benign | 4.27 | Benign | 0.25 | Tolerated | 0.3529 | 0.5842 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3937C>T | P1313S 2D AIThe SynGAP1 missense variant P1313S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the change as benign. No tool in the dataset predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. Overall, the collective evidence strongly suggests that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -4.279 | Likely Benign | 0.071 | Likely Benign | Likely Benign | 0.067 | Likely Benign | -0.03 | Neutral | 0.047 | Benign | 0.066 | Benign | 4.33 | Benign | 0.13 | Tolerated | 0.3520 | 0.6153 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3938C>A | P1313Q 2D  AIThe SynGAP1 missense variant P1313Q 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, is not available for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -4.533 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.063 | Likely Benign | 0.99 | Neutral | 0.324 | Benign | 0.287 | Benign | 4.31 | Benign | 0.15 | Tolerated | 0.1748 | 0.5651 | 0 | -1 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3938C>G | P1313R 2D AIThe SynGAP1 missense variant P1313R is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess pathogenicity are unanimous: all listed algorithms (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a benign effect, while none predict pathogenicity. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign,” and the protein‑folding stability tool Foldetta provides no result, so it does not influence the assessment. Based on the collective predictions, 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 | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -4.634 | Likely Benign | 0.161 | Likely Benign | Likely Benign | 0.088 | Likely Benign | -0.52 | Neutral | 0.324 | Benign | 0.172 | Benign | 4.25 | Benign | 0.22 | Tolerated | 0.1659 | 0.4742 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3938C>T | P1313L 2D AIThe SynGAP1 missense variant P1313L is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.970301 | Binding | 0.452 | 0.902 | 0.750 | -4.588 | Likely Benign | 0.097 | Likely Benign | Likely Benign | 0.082 | Likely Benign | 1.90 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.30 | Benign | 1.00 | Tolerated | 0.2489 | 0.6948 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| 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.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.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.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>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.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.3934G>A | A1312T 2D AISynGAP1 missense variant A1312T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available. Overall, the majority of evidence points to a benign effect, 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 | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | -4.137 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.155 | Likely Benign | -0.65 | Neutral | 0.991 | Probably Damaging | 0.989 | Probably Damaging | 3.17 | Benign | 0.00 | Affected | 0.1865 | 0.7600 | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3934G>C | A1312P 2D AIThe SynGAP1 missense variant A1312P 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 | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | -2.488 | Likely Benign | 0.076 | Likely Benign | Likely Benign | 0.222 | Likely Benign | -1.64 | Neutral | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 3.12 | Benign | 0.00 | Affected | 0.2208 | 0.5820 | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3934G>T | A1312S 2D AIThe SynGAP1 missense variant A1312S is reported in gnomAD (variant ID 6‑33451808‑G‑T) 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 predict a benign effect, while three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT) predict pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns “Benign” and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability data are available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is listed). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | 6-33451808-G-T | 1 | 6.21e-7 | -3.906 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.123 | Likely Benign | -1.03 | Neutral | 0.978 | Probably Damaging | 0.983 | Probably Damaging | 3.21 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2850 | 0.6211 | 1 | 1 | -2.6 | 16.00 | ||||||||||||||||||||||||||||||||||
| c.3935C>A | A1312D 2D AIThe SynGAP1 missense variant A1312D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence, particularly from the high‑accuracy tools, indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | -4.419 | Likely Benign | 0.398 | Ambiguous | Likely Benign | 0.272 | Likely Benign | -2.74 | Deleterious | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 3.11 | Benign | 0.00 | Affected | 0.2289 | 0.2993 | 0 | -2 | -5.3 | 44.01 | ||||||||||||||||||||||||||||||||||||||||
| c.3935C>G | A1312G 2D AIThe SynGAP1 missense variant A1312G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | -3.735 | Likely Benign | 0.097 | Likely Benign | Likely Benign | 0.157 | Likely Benign | -2.25 | Neutral | 0.978 | Probably Damaging | 0.983 | Probably Damaging | 3.15 | Benign | 0.00 | Affected | 0.2241 | 0.5058 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3935C>T | A1312V 2D AIThe SynGAP1 missense variant A1312V is reported in gnomAD (ID 6‑33451809‑C‑T) 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 predict a benign effect, while three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT) predict pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns “Benign” and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability data are available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is listed). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.767246 | Disordered | 0.971112 | Binding | 0.392 | 0.902 | 0.750 | 6-33451809-C-T | 4 | 2.48e-6 | -4.585 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.231 | Likely Benign | -1.74 | Neutral | 0.991 | Probably Damaging | 0.983 | Probably Damaging | 3.15 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1495 | 0.6343 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||
| c.3949G>A | G1317S 2D AIThe SynGAP1 missense variant G1317S is listed in ClinVar with an uncertain significance and is present in the gnomAD database. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized returns a benign prediction, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence overwhelmingly points to a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.908098 | Disordered | 0.971158 | Binding | 0.385 | 0.879 | 0.750 | Conflicting | 3 | 6-33451823-G-A | 1 | 6.26e-7 | -3.522 | Likely Benign | 0.145 | Likely Benign | Likely Benign | 0.092 | Likely Benign | -2.45 | Neutral | 0.127 | Benign | 0.045 | Benign | 4.08 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2546 | 0.4935 | 1 | 0 | -0.4 | 30.03 | ||||||||||||||||||||||||||||||||
| c.3949G>C | G1317R 2D AIThe SynGAP1 missense variant G1317R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and polyPhen‑2 HumVar, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 computational evidence overwhelmingly suggests that G1317R 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 | 0.908098 | Disordered | 0.971158 | Binding | 0.385 | 0.879 | 0.750 | -3.646 | Likely Benign | 0.619 | Likely Pathogenic | Likely Benign | 0.176 | Likely Benign | -2.17 | Neutral | 0.834 | Possibly Damaging | 0.307 | Benign | 4.04 | Benign | 0.00 | Affected | 0.1018 | 0.3791 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||||||
| 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.3950G>A | G1317D 2D AIThe SynGAP1 missense variant G1317D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451824‑G‑A). 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 is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction (2 benign vs. 1 pathogenic, with one uncertain). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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. | 0.908098 | Disordered | 0.971158 | Binding | 0.385 | 0.879 | 0.750 | 6-33451824-G-A | -4.860 | Likely Benign | 0.520 | Ambiguous | Likely Benign | 0.081 | Likely Benign | -3.54 | Deleterious | 0.588 | Possibly Damaging | 0.212 | Benign | 4.03 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2115 | 0.2859 | -1 | 1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||||
| c.3950G>C | G1317A 2D AIThe SynGAP1 missense variant G1317A is not 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, and this conclusion is consistent with the lack of ClinVar annotation. Thus, 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 | 0.908098 | Disordered | 0.971158 | Binding | 0.385 | 0.879 | 0.750 | -3.761 | Likely Benign | 0.190 | Likely Benign | Likely Benign | 0.049 | Likely Benign | -2.62 | Deleterious | 0.001 | Benign | 0.002 | Benign | 4.08 | Benign | 0.00 | Affected | 0.3582 | 0.4284 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3950G>T | G1317V 2D AIThe SynGAP1 missense variant G1317V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.908098 | Disordered | 0.971158 | Binding | 0.385 | 0.879 | 0.750 | -4.604 | Likely Benign | 0.286 | Likely Benign | Likely Benign | 0.050 | Likely Benign | -2.99 | Deleterious | 0.004 | Benign | 0.004 | Benign | 4.05 | Benign | 0.00 | Affected | 0.1132 | 0.3635 | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||||||
| c.3940C>A | P1314T 2D AIThe SynGAP1 missense variant P1314T is present in gnomAD (ID 6‑33451814‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | 6-33451814-C-A | -4.083 | Likely Benign | 0.096 | Likely Benign | Likely Benign | 0.066 | Likely Benign | 1.26 | Neutral | 0.061 | Benign | 0.045 | Benign | 4.32 | Benign | 0.97 | Tolerated | 3.77 | 5 | 0.1791 | 0.5626 | -1 | 0 | 0.9 | 3.99 | ||||||||||||||||||||||||||||||||||||
| c.3940C>G | P1314A 2D AIThe SynGAP1 missense variant P1314A is catalogued in gnomAD (ID 6‑33451814‑C‑G) but has no ClinVar entry. Across the spectrum of in silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—returns a benign or likely benign verdict. No pathogenic predictions appear in the dataset, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Taken together, the evidence overwhelmingly supports a benign classification, and this conclusion does not conflict 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 | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | 6-33451814-C-G | 1 | 6.22e-7 | -3.540 | Likely Benign | 0.061 | Likely Benign | Likely Benign | 0.043 | Likely Benign | -0.37 | Neutral | 0.001 | Benign | 0.002 | Benign | 4.23 | Benign | 0.93 | Tolerated | 3.77 | 5 | 0.3502 | 0.4441 | -1 | 1 | 3.4 | -26.04 | ||||||||||||||||||||||||||||||||||
| c.3940C>T | P1314S 2D AIThe SynGAP1 missense variant P1314S has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | -3.838 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.046 | Likely Benign | 0.11 | Neutral | 0.005 | Benign | 0.003 | Benign | 4.22 | Benign | 0.72 | Tolerated | 0.3522 | 0.4751 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3941C>A | P1314Q 2D AIThe SynGAP1 missense variant P1314Q is listed in gnomAD (ID 6‑33451815‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign. No Foldetta stability data are available, so folding‑stability evidence is unavailable. Overall, the preponderance of computational evidence indicates that P1314Q 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 | 0.882776 | Disordered | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | 6-33451815-C-A | -4.222 | Likely Benign | 0.104 | Likely Benign | Likely Benign | 0.039 | Likely Benign | -0.55 | Neutral | 0.618 | Possibly Damaging | 0.333 | Benign | 4.24 | Benign | 0.04 | Affected | 3.77 | 5 | 0.1612 | 0.4588 | -1 | 0 | -1.9 | 31.01 | ||||||||||||||||||||||||||||||||||||
| c.3941C>G | P1314R 2D AIThe SynGAP1 missense variant P1314R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | -4.234 | Likely Benign | 0.168 | Likely Benign | Likely Benign | 0.036 | Likely Benign | 0.01 | Neutral | 0.618 | Possibly Damaging | 0.206 | Benign | 4.25 | Benign | 0.09 | Tolerated | 0.1634 | 0.3405 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3941C>T | P1314L 2D AIThe SynGAP1 missense variant P1314L is listed in ClinVar as a benign alteration (ClinVar ID 646689.0) and is present in the gnomAD database (gnomAD ID 6‑33451815‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, which is consistent with the ClinVar classification. Thus, the variant is most likely benign and does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.971592 | Binding | 0.467 | 0.903 | 0.750 | Likely Benign | 1 | 6-33451815-C-T | 2 | 1.24e-6 | -4.040 | Likely Benign | 0.118 | Likely Benign | Likely Benign | 0.049 | Likely Benign | -0.20 | Neutral | 0.421 | Benign | 0.066 | Benign | 4.19 | Benign | 0.05 | Affected | 3.77 | 5 | 0.2310 | 0.5967 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||
| c.2770C>A | P924T 2D AIThe SynGAP1 missense variant P924T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P924T is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -6.360 | Likely Benign | 0.961 | Likely Pathogenic | Likely Pathogenic | 0.400 | Likely Benign | -6.03 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.67 | Pathogenic | 0.00 | Affected | 0.1190 | 0.4009 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.2770C>G | P924A 2D AIThe SynGAP1 missense variant P924A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments 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) has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -5.995 | Likely Benign | 0.854 | Likely Pathogenic | Ambiguous | 0.383 | Likely Benign | -5.90 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 0.68 | Pathogenic | 0.00 | Affected | 0.2904 | 0.3423 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.2770C>T | P924S 2D AIThe SynGAP1 missense variant P924S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect for P924S, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -4.686 | Likely Benign | 0.920 | Likely Pathogenic | Ambiguous | 0.388 | Likely Benign | -5.86 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.68 | Pathogenic | 0.00 | Affected | 0.2952 | 0.3772 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.2771C>A | P924H 2D AIThe SynGAP1 missense variant P924H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of computational evidence indicates that P924H is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -6.236 | Likely Benign | 0.957 | Likely Pathogenic | Likely Pathogenic | 0.457 | Likely Benign | -5.87 | Deleterious | 1.000 | Probably Damaging | 1.000 | Probably Damaging | 0.65 | Pathogenic | 0.00 | Affected | 0.1317 | 0.3281 | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2771C>G | P924R 2D AIThe SynGAP1 missense variant P924R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and ESM1b, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. Grouping by consensus, the pathogenic group outweighs the benign group. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta data are unavailable. Overall, the preponderance of evidence indicates that P924R 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 | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -6.024 | Likely Benign | 0.965 | Likely Pathogenic | Likely Pathogenic | 0.420 | Likely Benign | -6.20 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.66 | Pathogenic | 0.00 | Affected | 0.1314 | 0.2083 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.2771C>T | P924L 2D AIThe SynGAP1 missense variant P924L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P924L is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.521092 | Disordered | 0.971858 | Binding | 0.293 | 0.846 | 0.250 | -6.361 | Likely Benign | 0.971 | Likely Pathogenic | Likely Pathogenic | 0.422 | Likely Benign | -6.89 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.66 | Pathogenic | 0.00 | Affected | 0.1771 | 0.4941 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| 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.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.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.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.3947A>G | N1316S 2D  AIThe SynGAP1 missense variant N1316S is reported in gnomAD (ID 6‑33451821‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.971970 | Binding | 0.380 | 0.885 | 0.750 | 6-33451821-A-G | 1 | 6.25e-7 | -2.906 | Likely Benign | 0.169 | Likely Benign | Likely Benign | 0.084 | Likely Benign | -2.69 | Deleterious | 0.004 | Benign | 0.003 | Benign | 4.03 | Benign | 0.00 | Affected | 3.77 | 5 | 0.3937 | 0.6307 | 1 | 1 | 2.7 | -27.03 | ||||||||||||||||||||||||||||||||||
| 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.3948T>A | N1316K 2D  AIThe SynGAP1 missense variant N1316K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451822‑T‑A). 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; 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, and this conclusion does not contradict any ClinVar annotation (none). 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. | 0.899122 | Disordered | 0.971970 | Binding | 0.380 | 0.885 | 0.750 | 6-33451822-T-A | -3.815 | Likely Benign | 0.699 | Likely Pathogenic | Likely Benign | 0.044 | Likely Benign | -3.27 | Deleterious | 0.414 | Benign | 0.063 | Benign | 4.00 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2065 | 0.5500 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||
| c.3948T>G | N1316K 2D AIThe SynGAP1 missense variant N1316K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451822‑T‑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, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign + 2 pathogenic), 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 is currently unreported. 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 | 6-33451822-T-G | -3.815 | Likely Benign | 0.699 | Likely Pathogenic | Likely Benign | 0.044 | Likely Benign | -3.27 | Deleterious | 0.414 | Benign | 0.063 | Benign | 4.00 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2065 | 0.5500 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||
| c.3298G>A | G1100S 2D AIThe SynGAP1 missense variant G1100S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact for G1100S, 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 | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | -2.898 | Likely Benign | 0.100 | Likely Benign | Likely Benign | 0.114 | Likely Benign | -0.65 | Neutral | 0.943 | Possibly Damaging | 0.595 | Possibly Damaging | 2.10 | Pathogenic | 0.28 | Tolerated | 0.2501 | 0.5699 | 1 | 0 | -0.4 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3298G>C | G1100R 2D AIThe SynGAP1 missense variant G1100R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; 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 lean toward pathogenicity, and this does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.882776 | Disordered | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | -2.923 | Likely Benign | 0.603 | Likely Pathogenic | Likely Benign | 0.176 | Likely Benign | -2.05 | Neutral | 0.992 | Probably Damaging | 0.906 | Possibly Damaging | 1.92 | Pathogenic | 0.00 | Affected | 0.0986 | 0.5217 | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||||||||
| c.3298G>T | G1100C 2D AIThe SynGAP1 missense variant G1100C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | -6.488 | Likely Benign | 0.150 | Likely Benign | Likely Benign | 0.174 | Likely Benign | -2.25 | Neutral | 0.999 | Probably Damaging | 0.950 | Probably Damaging | 1.91 | Pathogenic | 0.00 | Affected | 0.1354 | 0.4768 | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||||||
| c.3299G>A | G1100D 2D AIThe SynGAP1 missense variant G1100D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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. | 0.882776 | Disordered | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | -5.235 | Likely Benign | 0.577 | Likely Pathogenic | Likely Benign | 0.141 | Likely Benign | -1.67 | Neutral | 0.049 | Benign | 0.030 | Benign | 1.93 | Pathogenic | 0.01 | Affected | 0.1924 | 0.3043 | 1 | -1 | -3.1 | 58.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3299G>C | G1100A 2D AIThe SynGAP1 missense variant G1100A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | -2.862 | Likely Benign | 0.107 | Likely Benign | Likely Benign | 0.146 | Likely Benign | -0.95 | Neutral | 0.943 | Possibly Damaging | 0.667 | Possibly Damaging | 2.01 | Pathogenic | 0.05 | Affected | 0.3442 | 0.5154 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3299G>T | G1100V 2D AIThe SynGAP1 missense variant G1100V is reported in gnomAD (variant ID 6‑33443851‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign); pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the balance of evidence favors a benign classification for G1100V, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.972009 | Binding | 0.360 | 0.865 | 0.875 | 6-33443851-G-T | 1 | 6.51e-7 | -2.362 | Likely Benign | 0.118 | Likely Benign | Likely Benign | 0.198 | Likely Benign | -2.43 | Neutral | 0.992 | Probably Damaging | 0.906 | Possibly Damaging | 1.93 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.1297 | 0.4036 | -3 | -1 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||||
| c.3058C>G | R1020G 2D AIThe SynGAP1 missense variant R1020G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, 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. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.852992 | Disordered | 0.972945 | Binding | 0.340 | 0.777 | 0.500 | -4.898 | Likely Benign | 0.868 | Likely Pathogenic | Ambiguous | 0.162 | Likely Benign | -4.26 | Deleterious | 0.990 | Probably Damaging | 0.894 | Possibly Damaging | 2.48 | Pathogenic | 0.00 | Affected | 0.3394 | 0.3721 | -3 | -2 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||||||||||
| c.3058C>T | R1020W 2D  AIThe SynGAP1 missense variant R1020W is catalogued in gnomAD (ID 6‑33443610‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available. Taken together, the preponderance of evidence indicates that R1020W is most likely pathogenic, and this conclusion does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.852992 | Disordered | 0.972945 | Binding | 0.340 | 0.777 | 0.500 | 6-33443610-C-T | 6 | 3.72e-6 | -9.378 | Likely Pathogenic | 0.829 | Likely Pathogenic | Ambiguous | 0.165 | Likely Benign | -4.14 | Deleterious | 1.000 | Probably Damaging | 0.986 | Probably Damaging | 2.44 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.1420 | 0.4373 | -3 | 2 | 3.6 | 30.03 | ||||||||||||||||||||||||||||||||||
| c.3059G>A | R1020Q 2D AIThe SynGAP1 missense variant R1020Q is catalogued in gnomAD (6‑33443611‑G‑A) 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), while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates “Likely Benign.” No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the collective predictions, 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 | 0.852992 | Disordered | 0.972945 | Binding | 0.340 | 0.777 | 0.500 | 6-33443611-G-A | 2 | 1.24e-6 | -3.753 | Likely Benign | 0.445 | Ambiguous | Likely Benign | 0.137 | Likely Benign | -2.19 | Neutral | 0.995 | Probably Damaging | 0.870 | Possibly Damaging | 2.52 | Benign | 0.00 | Affected | 3.77 | 5 | 0.3050 | 0.2997 | 1 | 1 | 1.0 | -28.06 | ||||||||||||||||||||||||||||||||||
| c.3059G>C | R1020P 2D AIThe SynGAP1 missense variant R1020P is listed in ClinVar (ID 3700393.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Pathogenic” (3 pathogenic vs. 1 benign votes). 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 evidence points to a pathogenic effect, 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 Pathogenic | 0.852992 | Disordered | 0.972945 | Binding | 0.340 | 0.777 | 0.500 | Uncertain | 1 | -3.491 | Likely Benign | 0.902 | Likely Pathogenic | Ambiguous | 0.205 | Likely Benign | -3.50 | Deleterious | 0.999 | Probably Damaging | 0.977 | Probably Damaging | 2.46 | Pathogenic | 0.00 | Affected | 0.2077 | 0.5109 | 0 | -2 | 2.9 | -59.07 | |||||||||||||||||||||||||||||||||||||
| c.3059G>T | R1020L 2D AISynGAP1 missense variant R1020L 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, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive; Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.972945 | Binding | 0.340 | 0.777 | 0.500 | Uncertain | 1 | -6.031 | Likely Benign | 0.907 | Likely Pathogenic | Ambiguous | 0.216 | Likely Benign | -4.03 | Deleterious | 0.990 | Probably Damaging | 0.921 | Probably Damaging | 2.50 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1898 | 0.5214 | -3 | -2 | 8.3 | -43.03 | ||||||||||||||||||||||||||||||||||||
| c.3292A>C | S1098R 2D  AIThe SynGAP1 missense variant S1098R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign predictions. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, and the SGM‑Consensus (majority vote) also indicates Benign. Foldetta results are not available, so no stability evidence is considered. Overall, the majority of computational evidence supports a benign impact for S1098R, 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 | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -4.583 | Likely Benign | 0.775 | Likely Pathogenic | Likely Benign | 0.127 | Likely Benign | -1.00 | Neutral | 0.586 | Possibly Damaging | 0.223 | Benign | 2.72 | Benign | 0.16 | Tolerated | 0.1053 | 0.4012 | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||||||
| c.3292A>G | S1098G 2D  AIThe SynGAP1 missense variant S1098G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the collective predictions strongly support a benign impact, and this conclusion is consistent with the lack of a ClinVar pathogenic classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -3.494 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.066 | Likely Benign | -0.39 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.72 | Benign | 0.57 | Tolerated | 0.2634 | 0.5206 | 1 | 0 | 0.4 | -30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3292A>T | S1098C 2D  AIThe SynGAP1 missense variant S1098C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -6.553 | Likely Benign | 0.106 | Likely Benign | Likely Benign | 0.094 | Likely Benign | -1.46 | Neutral | 0.938 | Possibly Damaging | 0.665 | Possibly Damaging | 2.65 | Benign | 0.12 | Tolerated | 0.1249 | 0.6233 | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||||||
| c.3293G>A | S1098N 2D  AIThe SynGAP1 missense variant S1098N is listed in ClinVar (ID 864704.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443845‑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. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign classification, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | Conflicting | 2 | 6-33443845-G-A | 6 | 3.89e-6 | -5.120 | Likely Benign | 0.156 | Likely Benign | Likely Benign | 0.063 | Likely Benign | -0.58 | Neutral | 0.369 | Benign | 0.120 | Benign | 2.76 | Benign | 0.36 | Tolerated | 3.77 | 5 | 0.1665 | 0.5145 | 1 | 1 | -2.7 | 27.03 | ||||||||||||||||||||||||||||||||
| c.3293G>C | S1098T 2D  AIThe SynGAP1 missense variant S1098T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, 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 | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -4.144 | Likely Benign | 0.073 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -0.18 | Neutral | 0.224 | Benign | 0.120 | Benign | 2.76 | Benign | 0.88 | Tolerated | 0.1706 | 0.6653 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3293G>T | S1098I 2D  AIThe SynGAP1 missense variant S1098I is catalogued in gnomAD (ID 6‑33443845‑G‑T) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | 6-33443845-G-T | -4.497 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.139 | Likely Benign | -0.92 | Neutral | 0.259 | Benign | 0.066 | Benign | 2.67 | Benign | 0.15 | Tolerated | 3.77 | 5 | 0.1219 | 0.5601 | -2 | -1 | 5.3 | 26.08 | ||||||||||||||||||||||||||||||||||||
| c.3294T>A | S1098R 2D AIThe SynGAP1 missense variant S1098R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv 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 support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is benign, and the protein‑folding stability method Foldetta is not available 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 | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -4.583 | Likely Benign | 0.775 | Likely Pathogenic | Likely Benign | 0.133 | Likely Benign | -1.00 | Neutral | 0.586 | Possibly Damaging | 0.223 | Benign | 2.72 | Benign | 0.16 | Tolerated | 0.1053 | 0.4012 | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||||||
| c.3294T>G | S1098R 2D AIThe SynGAP1 missense variant S1098R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv 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 support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is benign, and the protein‑folding stability method Foldetta is not available 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 | 0.973030 | Binding | 0.337 | 0.855 | 1.000 | -4.583 | Likely Benign | 0.775 | Likely Pathogenic | Likely Benign | 0.134 | Likely Benign | -1.00 | Neutral | 0.586 | Possibly Damaging | 0.223 | Benign | 2.72 | Benign | 0.16 | Tolerated | 0.1053 | 0.4012 | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||||||
| c.3943T>A | W1315R 2D  AIThe SynGAP1 missense variant W1315R is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. Only AlphaMissense‑Default predicts a pathogenic outcome, representing the sole discordant signal. 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 high‑accuracy tools points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | 0.205 | Likely Benign | 0.660 | Likely Pathogenic | Likely Benign | 0.114 | Likely Benign | 1.31 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.37 | Benign | 0.91 | Tolerated | 3.77 | 5 | 0.4317 | 0.0384 | 2 | -3 | -3.6 | -30.03 | |||||||||||||||||||||||||||||||||||||
| c.3943T>C | W1315R 2D AIThe SynGAP1 missense variant W1315R is listed in ClinVar (ID 1029092.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | Uncertain | 1 | 0.205 | Likely Benign | 0.660 | Likely Pathogenic | Likely Benign | 0.114 | Likely Benign | 1.31 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.37 | Benign | 0.91 | Tolerated | 3.77 | 5 | 0.4317 | 0.0384 | 2 | -3 | -3.6 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.3943T>G | W1315G 2D  AIThe SynGAP1 missense variant W1315G is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | 0.687 | Likely Benign | 0.193 | Likely Benign | Likely Benign | 0.113 | Likely Benign | -1.36 | Neutral | 0.208 | Benign | 0.077 | Benign | 4.21 | Benign | 0.12 | Tolerated | 0.4126 | 0.1745 | -7 | -2 | 0.5 | -129.16 | |||||||||||||||||||||||||||||||||||||||
| c.3944G>C | W1315S 2D  AIThe SynGAP1 missense variant W1315S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | 0.896 | Likely Benign | 0.279 | Likely Benign | Likely Benign | 0.118 | Likely Benign | -0.79 | Neutral | 0.115 | Benign | 0.057 | Benign | 4.26 | Benign | 0.13 | Tolerated | 0.3974 | 0.1211 | -2 | -3 | 0.1 | -99.14 | |||||||||||||||||||||||||||||||||||||||
| c.3944G>T | W1315L 2D  AIThe SynGAP1 missense variant W1315L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | 0.369 | Likely Benign | 0.304 | Likely Benign | Likely Benign | 0.066 | Likely Benign | -0.65 | Neutral | 0.115 | Benign | 0.057 | Benign | 4.29 | Benign | 0.16 | Tolerated | 0.2256 | 0.3338 | -2 | -2 | 4.7 | -73.05 | |||||||||||||||||||||||||||||||||||||||
| c.3945G>C | W1315C 2D  AIThe SynGAP1 missense variant W1315C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar) and SIFT, together with AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | -2.355 | Likely Benign | 0.671 | Likely Pathogenic | Likely Benign | 0.082 | Likely Benign | -1.54 | Neutral | 0.872 | Possibly Damaging | 0.468 | Possibly Damaging | 4.21 | Benign | 0.02 | Affected | 0.3427 | 0.1929 | -8 | -2 | 3.4 | -83.07 | |||||||||||||||||||||||||||||||||||||||
| c.3945G>T | W1315C 2D AIThe SynGAP1 missense variant W1315C 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 impact for W1315C, 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 | 0.885302 | Disordered | 0.973142 | Binding | 0.403 | 0.889 | 0.750 | -2.355 | Likely Benign | 0.671 | Likely Pathogenic | Likely Benign | 0.082 | Likely Benign | -1.54 | Neutral | 0.872 | Possibly Damaging | 0.468 | Possibly Damaging | 4.21 | Benign | 0.02 | Affected | 0.3427 | 0.1929 | -8 | -2 | 3.4 | -83.07 | |||||||||||||||||||||||||||||||||||||||
| c.2806G>A | A936T 2D AIThe SynGAP1 missense variant A936T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443358‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. 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 “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the computational evidence overwhelmingly indicates that the variant is most likely benign, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | Uncertain | 1 | 6-33443358-G-A | 1 | 6.20e-7 | -4.540 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.047 | Likely Benign | -0.50 | Neutral | 0.051 | Benign | 0.033 | Benign | 2.67 | Benign | 0.09 | Tolerated | 3.77 | 5 | 0.1693 | 0.7003 | 0 | 1 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||||
| c.2806G>C | A936P 2D AIThe SynGAP1 missense variant A936P is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all classify the change as benign or likely benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. No Foldetta stability prediction is available. Overall, the computational evidence overwhelmingly points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | -2.782 | Likely Benign | 0.191 | Likely Benign | Likely Benign | 0.014 | Likely Benign | -1.28 | Neutral | 0.012 | Benign | 0.011 | Benign | 2.46 | Pathogenic | 0.06 | Tolerated | 0.2043 | 0.6109 | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||||||
| c.2806G>T | A936S 2D AIThe SynGAP1 missense variant A936S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, 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 | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | -3.555 | Likely Benign | 0.065 | Likely Benign | Likely Benign | 0.057 | Likely Benign | -0.07 | Neutral | 0.022 | Benign | 0.008 | Benign | 2.53 | Benign | 0.11 | Tolerated | 0.2675 | 0.5300 | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2807C>A | A936D 2D AIThe SynGAP1 missense variant A936D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. This conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | -4.162 | Likely Benign | 0.686 | Likely Pathogenic | Likely Benign | 0.115 | Likely Benign | -1.63 | Neutral | 0.801 | Possibly Damaging | 0.339 | Benign | 2.48 | Pathogenic | 0.02 | Affected | 0.1778 | 0.1660 | 0 | -2 | -5.3 | 44.01 | ||||||||||||||||||||||||||||||||||||||||
| c.2807C>G | A936G 2D AIThe SynGAP1 missense variant A936G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign 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 | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | -2.720 | Likely Benign | 0.095 | Likely Benign | Likely Benign | 0.065 | Likely Benign | -1.34 | Neutral | 0.454 | Possibly Damaging | 0.192 | Benign | 2.48 | Pathogenic | 0.12 | Tolerated | 0.2380 | 0.4529 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2807C>T | A936V 2D AIThe SynGAP1 missense variant A936V is reported in gnomAD (ID 6‑33443359‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of predictions, including the high‑accuracy consensus, indicate that A936V 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 | 0.812494 | Disordered | 0.973218 | Binding | 0.319 | 0.874 | 0.625 | 6-33443359-C-T | 4 | 2.48e-6 | -4.787 | Likely Benign | 0.226 | Likely Benign | Likely Benign | 0.089 | Likely Benign | -1.58 | Neutral | 0.801 | Possibly Damaging | 0.192 | Benign | 2.48 | Pathogenic | 0.19 | Tolerated | 3.77 | 5 | 0.1586 | 0.6921 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||
| c.4006G>A | E1336K 2D  AIThe SynGAP1 missense variant E1336K is listed in ClinVar (ID 984837) with an “Uncertain” status and is present in gnomAD (6‑33451880‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic impact 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, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign effect, 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 | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | Conflicting | 3 | 6-33451880-G-A | 6 | 4.20e-6 | -4.697 | Likely Benign | 0.977 | Likely Pathogenic | Likely Pathogenic | 0.272 | Likely Benign | -2.44 | Neutral | 0.748 | Possibly Damaging | 0.079 | Benign | 3.23 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2630 | 0.7501 | 0 | 1 | -0.4 | -0.94 | ||||||||||||||||||||||||||||||||
| c.4006G>C | E1336Q 2D  AIThe SynGAP1 missense change E1336Q 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‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, 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, 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 | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | -4.113 | Likely Benign | 0.769 | Likely Pathogenic | Likely Benign | 0.159 | Likely Benign | -1.88 | Neutral | 0.731 | Possibly Damaging | 0.301 | Benign | 3.21 | Benign | 0.00 | Affected | 0.1432 | 0.7427 | 2 | 2 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||||||
| c.4007A>C | E1336A 2D  AIThe SynGAP1 missense variant E1336A is not 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. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. This prediction does not contradict any ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | -3.545 | Likely Benign | 0.879 | Likely Pathogenic | Ambiguous | 0.191 | Likely Benign | -3.78 | Deleterious | 0.345 | Benign | 0.099 | Benign | 3.22 | Benign | 0.00 | Affected | 0.4000 | 0.7385 | 0 | -1 | 5.3 | -58.04 | ||||||||||||||||||||||||||||||||||||||||
| c.4007A>G | E1336G 2D  AIThe SynGAP1 missense variant E1336G is not 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. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta, which would assess protein‑folding stability, has no available result for this variant. Overall, the balance of evidence (five benign vs three pathogenic predictions) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | -3.574 | Likely Benign | 0.932 | Likely Pathogenic | Ambiguous | 0.211 | Likely Benign | -4.36 | Deleterious | 0.345 | Benign | 0.109 | Benign | 3.20 | Benign | 0.00 | Affected | 0.3092 | 0.6170 | 0 | -2 | 3.1 | -72.06 | ||||||||||||||||||||||||||||||||||||||||
| c.4007A>T | E1336V 2D  AIThe SynGAP1 missense variant E1336V has no ClinVar record (ClinVar status: None) and is not present in gnomAD (gnomAD ID: None). 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. AlphaMissense‑Optimized is reported as uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a tie (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic calls and no evidence from ClinVar to contradict this uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | -3.367 | Likely Benign | 0.932 | Likely Pathogenic | Ambiguous | 0.221 | Likely Benign | -4.46 | Deleterious | 0.789 | Possibly Damaging | 0.348 | Benign | 3.18 | Benign | 0.00 | Affected | 0.0991 | 0.7425 | -2 | -2 | 7.7 | -29.98 | ||||||||||||||||||||||||||||||||||||||||
| c.4008G>C | E1336D 2D  AIThe SynGAP1 missense variant E1336D is listed in ClinVar (ID 3323942.0) 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, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a 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, consistent with the ClinVar benign designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | Likely Benign | 1 | -3.344 | Likely Benign | 0.596 | Likely Pathogenic | Likely Benign | 0.062 | Likely Benign | -1.92 | Neutral | 0.001 | Benign | 0.003 | Benign | 3.30 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1995 | 0.5101 | 2 | 3 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.4008G>T | E1336D 2D AIThe SynGAP1 missense variant E1336D is catalogued in gnomAD (ID 6‑33451882‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. Only two tools—SIFT and AlphaMissense‑Default—predict pathogenicity. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also 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 preponderance of evidence points to a benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.973342 | Binding | 0.336 | 0.717 | 0.750 | 6-33451882-G-T | -3.344 | Likely Benign | 0.596 | Likely Pathogenic | Likely Benign | 0.065 | Likely Benign | -1.92 | Neutral | 0.001 | Benign | 0.003 | Benign | 3.30 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1995 | 0.5101 | 2 | 3 | 0.0 | -14.03 | ||||||||||||||||||||||||||||||||||||
| c.3118G>A | G1040S 2D AIThe SynGAP1 missense variant G1040S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, SIFT, and FATHMM. 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 (six benign versus four pathogenic predictions) points to a benign impact for G1040S. 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 | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | -2.179 | Likely Benign | 0.307 | Likely Benign | Likely Benign | 0.653 | Likely Pathogenic | -1.81 | Neutral | 0.827 | Possibly Damaging | 0.375 | Benign | -0.74 | Pathogenic | 0.02 | Affected | 0.2332 | 0.5298 | 1 | 0 | -0.4 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3118G>C | G1040R 2D AIThe SynGAP1 missense variant G1040R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to polyPhen‑2 HumVar and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence supports a pathogenic classification, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | -2.901 | Likely Benign | 0.949 | Likely Pathogenic | Ambiguous | 0.704 | Likely Pathogenic | -3.00 | Deleterious | 0.463 | Possibly Damaging | 0.194 | Benign | -0.74 | Pathogenic | 0.00 | Affected | 0.0924 | 0.4415 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||||||
| c.3118G>T | G1040C 2D AIThe SynGAP1 missense variant G1040C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict pathogenicity, while ESM1b and AlphaMissense‑Optimized predict a benign outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign prediction, whereas the SGM‑Consensus remains Likely Pathogenic; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | -6.272 | Likely Benign | 0.620 | Likely Pathogenic | Likely Benign | 0.744 | Likely Pathogenic | -3.04 | Deleterious | 0.999 | Probably Damaging | 0.917 | Probably Damaging | -0.74 | Pathogenic | 0.00 | Affected | 0.1155 | 0.4556 | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||||||
| c.3119G>A | G1040D 2D AIThe SynGAP1 missense variant G1040D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The high‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that G1040D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | -4.154 | Likely Benign | 0.956 | Likely Pathogenic | Likely Pathogenic | 0.761 | Likely Pathogenic | -2.82 | Deleterious | 0.986 | Probably Damaging | 0.787 | Possibly Damaging | -0.74 | Pathogenic | 0.00 | Affected | 0.1677 | 0.2042 | 1 | -1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||||||
| c.3119G>C | G1040A 2D AIThe SynGAP1 missense variant G1040A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL and FATHMM, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign prediction (2 benign vs. 1 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 any ClinVar annotation, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | -2.625 | Likely Benign | 0.409 | Ambiguous | Likely Benign | 0.606 | Likely Pathogenic | -1.65 | Neutral | 0.114 | Benign | 0.030 | Benign | -0.74 | Pathogenic | 0.30 | Tolerated | 0.3246 | 0.5331 | 1 | 0 | 2.2 | 14.03 | ||||||||||||||||||||||||||||||||||||||||
| c.3119G>T | G1040V 2D AIThe SynGAP1 missense variant G1040V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443671‑G‑T). Prediction tools that agree on a benign effect are ESM1b and AlphaMissense‑Optimized; those that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.964893 | Disordered | 0.973805 | Binding | 0.332 | 0.816 | 0.625 | Uncertain | 1 | 6-33443671-G-T | 4 | 2.48e-6 | -3.453 | Likely Benign | 0.645 | Likely Pathogenic | Likely Benign | 0.774 | Likely Pathogenic | -2.89 | Deleterious | 0.827 | Possibly Damaging | 0.456 | Possibly Damaging | -0.74 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.1239 | 0.4213 | -1 | -3 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||
| c.3295T>A | Y1099N 2D AIThe SynGAP1 missense variant Y1099N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | -4.329 | Likely Benign | 0.269 | Likely Benign | Likely Benign | 0.143 | Likely Benign | -1.01 | Neutral | 0.818 | Possibly Damaging | 0.360 | Benign | 2.83 | Benign | 0.16 | Tolerated | 0.2121 | 0.0935 | -2 | -2 | -2.2 | -49.07 | |||||||||||||||||||||||||||||||||||||||
| c.3295T>C | Y1099H 2D AIThe SynGAP1 missense variant Y1099H is reported in gnomAD (variant ID 6-33443847‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this 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 | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | 6-33443847-T-C | 1 | 6.49e-7 | -3.620 | Likely Benign | 0.267 | Likely Benign | Likely Benign | 0.123 | Likely Benign | -0.50 | Neutral | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.76 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.2453 | 0.0735 | 2 | 0 | -1.9 | -26.03 | ||||||||||||||||||||||||||||||||||
| c.3295T>G | Y1099D 2D AIThe SynGAP1 missense variant Y1099D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score the change as tolerated or benign, while only polyPhen‑2 HumDiv flags it as pathogenic. 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 is Likely Benign, and Foldetta results are unavailable. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | -4.193 | Likely Benign | 0.429 | Ambiguous | Likely Benign | 0.130 | Likely Benign | -1.08 | Neutral | 0.818 | Possibly Damaging | 0.435 | Benign | 2.79 | Benign | 0.13 | Tolerated | 0.3819 | 0.0935 | -4 | -3 | -2.2 | -48.09 | |||||||||||||||||||||||||||||||||||||||
| c.3296A>C | Y1099S 2D AIThe SynGAP1 missense variant Y1099S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | -1.775 | Likely Benign | 0.139 | Likely Benign | Likely Benign | 0.156 | Likely Benign | -0.23 | Neutral | 0.149 | Benign | 0.026 | Benign | 2.90 | Benign | 0.62 | Tolerated | 0.4564 | 0.2298 | -3 | -2 | 0.5 | -76.10 | |||||||||||||||||||||||||||||||||||||||
| c.3296A>G | Y1099C 2D AIThe SynGAP1 missense variant Y1099C is reported in gnomAD (variant ID 6‑33443848‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | 6-33443848-A-G | 3 | 1.95e-6 | -5.670 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.122 | Likely Benign | -1.13 | Neutral | 0.997 | Probably Damaging | 0.840 | Possibly Damaging | 2.73 | Benign | 0.14 | Tolerated | 3.77 | 5 | 0.3008 | 0.2382 | -2 | 0 | 3.8 | -60.04 | ||||||||||||||||||||||||||||||||||
| c.3296A>T | Y1099F 2D AIThe SynGAP1 missense variant Y1099F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this 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 | 0.885302 | Disordered | 0.974267 | Binding | 0.400 | 0.862 | 1.000 | -3.651 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.082 | Likely Benign | -0.85 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.75 | Benign | 0.27 | Tolerated | 0.2453 | 0.2780 | 7 | 3 | 4.1 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2938C>A | H980N 2D AIThe SynGAP1 missense variant H980N is not reported in ClinVar or gnomAD. Functional prediction tools largely agree on a benign effect. Benign calls come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus confirms a benign result; Foldetta data are unavailable, so no additional stability evidence is considered. Overall, the computational evidence indicates that H980N is most likely benign, 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 Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -4.728 | Likely Benign | 0.291 | Likely Benign | Likely Benign | 0.070 | Likely Benign | -1.07 | Neutral | 0.451 | Benign | 0.209 | Benign | 4.17 | Benign | 0.00 | Affected | 0.2346 | 0.3638 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2938C>G | H980D 2D AIThe SynGAP1 missense variant H980D is not reported 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. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational 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 | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -5.489 | Likely Benign | 0.729 | Likely Pathogenic | Likely Benign | 0.117 | Likely Benign | -1.38 | Neutral | 0.451 | Benign | 0.265 | Benign | 4.18 | Benign | 0.00 | Affected | 0.2608 | 0.3066 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2938C>T | H980Y 2D AIThe SynGAP1 missense variant H980Y 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 assessment. Overall, the majority of evidence points to a benign effect for H980Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -4.104 | Likely Benign | 0.299 | Likely Benign | Likely Benign | 0.083 | Likely Benign | -1.12 | Neutral | 0.925 | Possibly Damaging | 0.529 | Possibly Damaging | 4.13 | Benign | 0.00 | Affected | 0.1524 | 0.4706 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2939A>C | H980P 2D AIThe SynGAP1 missense variant H980P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools largely favor a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, two tools—polyPhen‑2 HumDiv and SIFT—classify the change as pathogenic. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus (majority vote) is likely benign; no Foldetta stability data are available. Overall, the preponderance of evidence points to a benign effect for H980P, and this conclusion is not in conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -3.071 | Likely Benign | 0.151 | Likely Benign | Likely Benign | 0.136 | Likely Benign | -1.70 | Neutral | 0.802 | Possibly Damaging | 0.432 | Benign | 4.15 | Benign | 0.00 | Affected | 0.2274 | 0.4301 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2939A>G | H980R 2D AIThe SynGAP1 missense variant H980R is listed in gnomAD (ID 6‑33443491‑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; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | 6-33443491-A-G | 1 | 6.20e-7 | -2.736 | Likely Benign | 0.409 | Ambiguous | Likely Benign | 0.095 | Likely Benign | -1.44 | Neutral | 0.802 | Possibly Damaging | 0.354 | Benign | 4.17 | Benign | 0.00 | Affected | 4.32 | 1 | 0.2439 | 0.3810 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||||
| c.2939A>T | H980L 2D AIThe SynGAP1 missense variant H980L is not reported 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. The variant is most likely benign, and this conclusion 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 | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -1.984 | Likely Benign | 0.293 | Likely Benign | Likely Benign | 0.187 | Likely Benign | -1.98 | Neutral | 0.625 | Possibly Damaging | 0.265 | Benign | 4.16 | Benign | 0.00 | Affected | 0.1488 | 0.5538 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2940T>A | H980Q 2D AIThe SynGAP1 missense variant H980Q is not reported 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 H980Q, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -4.014 | Likely Benign | 0.385 | Ambiguous | Likely Benign | 0.090 | Likely Benign | -1.35 | Neutral | 0.802 | Possibly Damaging | 0.432 | Benign | 4.18 | Benign | 0.00 | Affected | 0.2236 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2940T>G | H980Q 2D AIThe SynGAP1 missense variant H980Q is not reported 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 H980Q, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.812494 | Disordered | 0.974598 | Binding | 0.309 | 0.892 | 0.625 | -4.014 | Likely Benign | 0.385 | Ambiguous | Likely Benign | 0.090 | Likely Benign | -1.35 | Neutral | 0.802 | Possibly Damaging | 0.432 | Benign | 4.18 | Benign | 0.00 | Affected | 0.2236 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2896C>A | H966N 2D AIThe SynGAP1 missense variant H966N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while ESM1b 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that H966N 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 | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | -7.579 | In-Between | 0.085 | Likely Benign | Likely Benign | 0.094 | Likely Benign | -0.84 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.89 | Tolerated | 0.2153 | 0.3788 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2896C>G | H966D 2D AIThe SynGAP1 missense variant H966D is listed in gnomAD (ID 6‑33443448‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, 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 two tools predict a damaging outcome—polyPhen‑2 HumDiv and ESM1b—which are outliers relative to the consensus. High‑accuracy assessments confirm the benign trend: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus also indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a pathogenic ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | 6-33443448-C-G | 1 | 6.20e-7 | -8.426 | Likely Pathogenic | 0.201 | Likely Benign | Likely Benign | 0.182 | Likely Benign | -1.09 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.05 | Benign | 0.93 | Tolerated | 4.32 | 2 | 0.2504 | 0.3066 | -1 | 1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||||||
| c.2896C>T | H966Y 2D AIThe SynGAP1 missense variant H966Y is catalogued in gnomAD (6‑33443448‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all classify the change as benign or likely benign. Only polyPhen‑2 HumDiv reports a pathogenic prediction, representing the sole discordant signal. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. No Foldetta stability data are available, so folding‑stability evidence is inconclusive. Overall, the preponderance of predictions supports a benign classification for H966Y, and this conclusion is not contradicted by any ClinVar status (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | 6-33443448-C-T | -6.847 | Likely Benign | 0.126 | Likely Benign | Likely Benign | 0.106 | Likely Benign | -1.27 | Neutral | 0.878 | Possibly Damaging | 0.232 | Benign | 4.01 | Benign | 0.23 | Tolerated | 4.32 | 2 | 0.1465 | 0.4506 | 2 | 0 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||||
| c.2897A>C | H966P 2D AIThe SynGAP1 missense variant H966P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | -5.831 | Likely Benign | 0.064 | Likely Benign | Likely Benign | 0.279 | Likely Benign | -0.27 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.01 | Benign | 0.72 | Tolerated | 0.2168 | 0.4301 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2897A>G | H966R 2D AIThe SynGAP1 missense variant H966R is reported in gnomAD (ID 6‑33443449‑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 predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that H966R 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 | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | 6-33443449-A-G | -5.474 | Likely Benign | 0.157 | Likely Benign | Likely Benign | 0.172 | Likely Benign | -0.71 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.06 | Benign | 0.69 | Tolerated | 4.32 | 2 | 0.2198 | 0.3410 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||||||
| c.2897A>T | H966L 2D AIThe SynGAP1 missense variant H966L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present among the evaluated algorithms. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign. Foldetta results are not available for this variant. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | -6.119 | Likely Benign | 0.095 | Likely Benign | Likely Benign | 0.183 | Likely Benign | -1.74 | Neutral | 0.174 | Benign | 0.062 | Benign | 4.05 | Benign | 0.35 | Tolerated | 0.1514 | 0.5316 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2898C>A | H966Q 2D AIThe SynGAP1 missense variant H966Q is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that H966Q 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 | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | -5.662 | Likely Benign | 0.100 | Likely Benign | Likely Benign | 0.113 | Likely Benign | -0.66 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.45 | Tolerated | 0.2058 | 0.3914 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2898C>G | H966Q 2D AIThe SynGAP1 missense variant H966Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.976962 | Disordered | 0.974672 | Binding | 0.378 | 0.879 | 0.750 | -5.662 | Likely Benign | 0.100 | Likely Benign | Likely Benign | 0.113 | Likely Benign | -0.66 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.45 | Tolerated | 0.2058 | 0.3914 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3259T>A | S1087T 2D AIThe SynGAP1 missense variant S1087T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | -4.455 | Likely Benign | 0.128 | Likely Benign | Likely Benign | 0.044 | Likely Benign | -1.01 | Neutral | 0.790 | Possibly Damaging | 0.266 | Benign | 2.66 | Benign | 0.25 | Tolerated | 0.1333 | 0.6503 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3259T>C | S1087P 2D  AIThe SynGAP1 missense variant S1087P is reported in gnomAD (ID 6‑33443811‑T‑C) and has no ClinVar entry. All available in silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Based on the unanimous benign predictions and lack of ClinVar pathogenic annotation, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | 6-33443811-T-C | 1 | 6.34e-7 | -2.946 | Likely Benign | 0.133 | Likely Benign | Likely Benign | 0.135 | Likely Benign | -1.92 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.56 | Benign | 0.12 | Tolerated | 3.77 | 5 | 0.1803 | 0.5700 | -1 | 1 | -0.8 | 10.04 | ||||||||||||||||||||||||||||||||||
| c.3259T>G | S1087A 2D  AIThe SynGAP1 missense variant S1087A is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the consensus of all available 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 | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | -3.649 | Likely Benign | 0.076 | Likely Benign | Likely Benign | 0.057 | Likely Benign | -1.03 | Neutral | 0.447 | Benign | 0.139 | Benign | 2.64 | Benign | 0.34 | Tolerated | 0.4464 | 0.5405 | 1 | 1 | 2.6 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3260C>A | S1087Y 2D  AIThe SynGAP1 missense variant S1087Y is catalogued in gnomAD (ID 6‑33443812‑C‑A) and has no ClinVar entry. 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, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as benign, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, 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 | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | 6-33443812-C-A | -4.194 | Likely Benign | 0.587 | Likely Pathogenic | Likely Benign | 0.107 | Likely Benign | -2.41 | Neutral | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.56 | Benign | 0.02 | Affected | 3.77 | 5 | 0.0671 | 0.5845 | -2 | -3 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||||||
| c.3260C>G | S1087C 2D AIThe SynGAP1 missense variant S1087C is catalogued in gnomAD (ID 6‑33443812‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion 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 | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | 6-33443812-C-G | 1 | 6.34e-7 | -7.369 | In-Between | 0.194 | Likely Benign | Likely Benign | 0.083 | Likely Benign | -2.22 | Neutral | 0.997 | Probably Damaging | 0.840 | Possibly Damaging | 2.55 | Benign | 0.05 | Affected | 3.77 | 5 | 0.0979 | 0.6118 | -1 | 0 | 3.3 | 16.06 | ||||||||||||||||||||||||||||||||||
| c.3260C>T | S1087F 2D  AISynGAP1 missense variant S1087F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of reliable predictors and the two high‑accuracy tools suggest a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.912647 | Disordered | 0.974805 | Binding | 0.357 | 0.891 | 1.000 | Uncertain | 1 | -3.843 | Likely Benign | 0.497 | Ambiguous | Likely Benign | 0.105 | Likely Benign | -2.75 | Deleterious | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.56 | Benign | 0.03 | Affected | 3.77 | 5 | 0.0645 | 0.6029 | -2 | -3 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||
| c.3289C>A | P1097T 2D AIThe SynGAP1 missense variant P1097T is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the computational evidence strongly supports a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | -5.000 | Likely Benign | 0.097 | Likely Benign | Likely Benign | 0.110 | Likely Benign | -1.38 | Neutral | 0.009 | Benign | 0.013 | Benign | 2.61 | Benign | 0.21 | Tolerated | 0.1751 | 0.6567 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3289C>G | P1097A 2D AIThe SynGAP1 missense variant P1097A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The high‑accuracy consensus (SGM‑Consensus, derived from 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. Based on the unanimous benign predictions and the lack of any pathogenic evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | -4.315 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.059 | Likely Benign | -1.77 | Neutral | 0.245 | Benign | 0.140 | Benign | 2.71 | Benign | 0.26 | Tolerated | 0.3199 | 0.5381 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3289C>T | P1097S 2D AIThe SynGAP1 missense variant P1097S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | -3.748 | Likely Benign | 0.116 | Likely Benign | Likely Benign | 0.053 | Likely Benign | -1.04 | Neutral | 0.025 | Benign | 0.023 | Benign | 2.62 | Benign | 0.70 | Tolerated | 0.3332 | 0.5691 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3290C>A | P1097Q 2D AIThe SynGAP1 missense variant P1097Q is reported in gnomAD (ID 6‑33443842‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign 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 | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | 6-33443842-C-A | -4.765 | Likely Benign | 0.198 | Likely Benign | Likely Benign | 0.092 | Likely Benign | -1.10 | Neutral | 0.918 | Possibly Damaging | 0.604 | Possibly Damaging | 2.58 | Benign | 0.12 | Tolerated | 3.77 | 5 | 0.1613 | 0.5136 | -1 | 0 | -1.9 | 31.01 | ||||||||||||||||||||||||||||||||||||
| c.3290C>G | P1097R 2D AIThe SynGAP1 missense variant P1097R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the preponderance of benign predictions and the lack of pathogenic evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | -4.938 | Likely Benign | 0.422 | Ambiguous | Likely Benign | 0.079 | Likely Benign | -1.75 | Neutral | 0.918 | Possibly Damaging | 0.525 | Possibly Damaging | 2.58 | Benign | 0.07 | Tolerated | 0.1517 | 0.4027 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3290C>T | P1097L 2D AIThe SynGAP1 missense variant P1097L is listed in ClinVar as Benign (ClinVar ID 2060978.0) and is not reported in gnomAD. 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 from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign impact, and this conclusion is consistent with the ClinVar designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.974957 | Binding | 0.384 | 0.858 | 1.000 | Benign | 1 | -4.410 | Likely Benign | 0.145 | Likely Benign | Likely Benign | 0.131 | Likely Benign | -2.07 | Neutral | 0.611 | Possibly Damaging | 0.198 | Benign | 2.64 | Benign | 0.05 | Affected | 3.77 | 5 | 0.2349 | 0.6356 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||
| c.2926T>A | F976I 2D  AIThe SynGAP1 missense variant F976I 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -4.595 | Likely Benign | 0.364 | Ambiguous | Likely Benign | 0.148 | Likely Benign | -1.16 | Neutral | 0.666 | Possibly Damaging | 0.265 | Benign | 4.16 | Benign | 0.21 | Tolerated | 0.2790 | 0.2714 | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2926T>C | F976L 2D  AIThe SynGAP1 missense variant F976L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as “Likely Benign.” In contrast, AlphaMissense‑Default predicts a pathogenic effect, while AlphaMissense‑Optimized is uncertain. No Foldetta (FoldX‑MD/ Rosetta) stability result is available, so it does not contribute to the assessment. Overall, the majority of high‑confidence predictors indicate 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. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -2.432 | Likely Benign | 0.825 | Likely Pathogenic | Ambiguous | 0.237 | Likely Benign | -0.87 | Neutral | 0.264 | Benign | 0.102 | Benign | 4.20 | Benign | 0.53 | Tolerated | 4.32 | 2 | 0.2829 | 0.3082 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||
| c.2926T>G | F976V 2D  AIThe SynGAP1 missense variant F976V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -3.328 | Likely Benign | 0.268 | Likely Benign | Likely Benign | 0.190 | Likely Benign | -1.32 | Neutral | 0.451 | Benign | 0.157 | Benign | 4.18 | Benign | 0.23 | Tolerated | 0.2696 | 0.2902 | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||||||
| c.2927T>A | F976Y 2D  AIThe SynGAP1 missense variant F976Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -3.902 | Likely Benign | 0.225 | Likely Benign | Likely Benign | 0.172 | Likely Benign | -0.50 | Neutral | 0.925 | Possibly Damaging | 0.529 | Possibly Damaging | 4.11 | Benign | 0.80 | Tolerated | 0.1942 | 0.2257 | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2927T>C | F976S 2D  AIThe SynGAP1 missense variant F976S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Based on the collective 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 | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -2.393 | Likely Benign | 0.432 | Ambiguous | Likely Benign | 0.217 | Likely Benign | -0.73 | Neutral | 0.292 | Benign | 0.102 | Benign | 4.16 | Benign | 0.49 | Tolerated | 0.4432 | 0.1134 | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||||||
| c.2927T>G | F976C 2D  AIThe SynGAP1 missense variant F976C is not reported in ClinVar and is absent from gnomAD. In silico predictors cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for F976C, and this conclusion is not in conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | -5.490 | Likely Benign | 0.490 | Ambiguous | Likely Benign | 0.103 | Likely Benign | -1.10 | Neutral | 0.977 | Probably Damaging | 0.840 | Possibly Damaging | 4.09 | Benign | 0.10 | Tolerated | 0.2961 | 0.2505 | -4 | -2 | -0.3 | -44.04 | |||||||||||||||||||||||||||||||||||||||
| c.2928T>A | F976L 2D AIThe SynGAP1 missense variant F976L is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443480‑T‑A). 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, 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 preponderance of evidence from high‑accuracy predictors and consensus analysis indicates that F976L 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 | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | 6-33443480-T-A | 2 | 1.24e-6 | -2.432 | Likely Benign | 0.825 | Likely Pathogenic | Ambiguous | 0.212 | Likely Benign | -0.87 | Neutral | 0.264 | Benign | 0.102 | Benign | 4.20 | Benign | 0.53 | Tolerated | 4.32 | 2 | 0.2829 | 0.3082 | 2 | 0 | 1.0 | -34.02 | ||||||||||||||||||||||||||||||||||
| c.2928T>G | F976L 2D AIThe SynGAP1 missense variant F976L is listed in ClinVar (ID 624245.0) 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), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome. The high‑accuracy consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. AlphaMissense‑Optimized is inconclusive, and no Foldetta (FoldX‑MD/Rosetta stability) result is available. 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 predictions do not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.975061 | Binding | 0.311 | 0.894 | 0.625 | Uncertain | 1 | -2.432 | Likely Benign | 0.825 | Likely Pathogenic | Ambiguous | 0.212 | Likely Benign | -0.87 | Neutral | 0.264 | Benign | 0.102 | Benign | 4.20 | Benign | 0.53 | Tolerated | 4.32 | 2 | 0.2829 | 0.3082 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.3199C>A | P1067T 2D AIThe SynGAP1 missense variant P1067T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.898 | Likely Benign | 0.084 | Likely Benign | Likely Benign | 0.062 | Likely Benign | -1.94 | Neutral | 0.827 | Possibly Damaging | 0.375 | Benign | 2.79 | Benign | 0.04 | Affected | 0.1449 | 0.6132 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3199C>G | P1067A 2D AIThe SynGAP1 missense variant P1067A 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, representing the sole discordant prediction. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: 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 preponderance of evidence supports a benign classification for P1067A, 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 | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.639 | Likely Benign | 0.052 | Likely Benign | Likely Benign | 0.073 | Likely Benign | -2.05 | Neutral | 0.664 | Possibly Damaging | 0.283 | Benign | 2.87 | Benign | 0.07 | Tolerated | 0.3097 | 0.5322 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3199C>T | P1067S 2D AIThe SynGAP1 missense variant P1067S is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.673 | Likely Benign | 0.073 | Likely Benign | Likely Benign | 0.079 | Likely Benign | -1.43 | Neutral | 0.271 | Benign | 0.054 | Benign | 2.91 | Benign | 0.48 | Tolerated | 0.3086 | 0.5753 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3200C>A | P1067Q 2D AIThe SynGAP1 missense variant P1067Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for P1067Q, 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 | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.767 | Likely Benign | 0.114 | Likely Benign | Likely Benign | 0.136 | Likely Benign | -2.39 | Neutral | 0.463 | Possibly Damaging | 0.087 | Benign | 2.84 | Benign | 0.01 | Affected | 0.1369 | 0.5415 | 0 | -1 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3200C>G | P1067R 2D AIThe SynGAP1 missense variant P1067R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta’s stability analysis is unavailable. Taken together, the majority of reliable predictors and the high‑accuracy tools indicate a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.878 | Likely Benign | 0.376 | Ambiguous | Likely Benign | 0.167 | Likely Benign | -2.74 | Deleterious | 0.971 | Probably Damaging | 0.580 | Possibly Damaging | 2.78 | Benign | 0.01 | Affected | 0.1300 | 0.3651 | 0 | -2 | -2.9 | 59.07 | ||||||||||||||||||||||||||||||||||||||||
| c.3200C>T | P1067L 2D AIThe SynGAP1 missense variant P1067L is not 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 predictions and the consensus analysis indicate a benign impact. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.966441 | Disordered | 0.975099 | Binding | 0.459 | 0.907 | 0.875 | -4.461 | Likely Benign | 0.107 | Likely Benign | Likely Benign | 0.157 | Likely Benign | -3.01 | Deleterious | 0.951 | Possibly Damaging | 0.619 | Possibly Damaging | 2.76 | Benign | 0.01 | Affected | 0.2047 | 0.6198 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| c.3262A>C | S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized labels the variant as Pathogenic, but the SGM‑Consensus (majority vote) remains Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect; this conclusion does not conflict with ClinVar, which contains no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | -4.588 | Likely Benign | 0.988 | Likely Pathogenic | Likely Pathogenic | 0.209 | Likely Benign | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1190 | 0.4502 | -1 | 0 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||||
| c.3262A>G | S1088G 2D AIThe SynGAP1 missense variant S1088G is listed in ClinVar (ID 2742833.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as Likely Benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | Uncertain | 1 | -5.034 | Likely Benign | 0.285 | Likely Benign | Likely Benign | 0.163 | Likely Benign | -1.83 | Neutral | 0.979 | Probably Damaging | 0.973 | Probably Damaging | 2.63 | Benign | 0.03 | Affected | 3.77 | 5 | 0.2541 | 0.5170 | 0 | 1 | 0.4 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.3262A>T | S1088C 2D AIThe SynGAP1 missense variant S1088C is not 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 and HumVar) and SIFT. 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 contains two benign and two uncertain calls, and Foldetta data 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. | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | -7.532 | In-Between | 0.547 | Ambiguous | Likely Benign | 0.212 | Likely Benign | -2.33 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.59 | Benign | 0.01 | Affected | 0.1571 | 0.6166 | 0 | -1 | 3.3 | 16.06 | ||||||||||||||||||||||||||||||||||||||||
| c.3263G>A | S1088N 2D AIThe SynGAP1 missense variant S1088N has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, while the SGM‑Consensus (derived from the four high‑accuracy tools) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign impact, 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 | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | -5.227 | Likely Benign | 0.791 | Likely Pathogenic | Ambiguous | 0.155 | Likely Benign | -1.25 | Neutral | 0.991 | Probably Damaging | 0.982 | Probably Damaging | 2.69 | Benign | 0.02 | Affected | 0.1940 | 0.5197 | 1 | 1 | -2.7 | 27.03 | |||||||||||||||||||||||||||||||||||||||
| c.3263G>C | S1088T 2D AIThe SynGAP1 missense variant S1088T 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 conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | -4.569 | Likely Benign | 0.295 | Likely Benign | Likely Benign | 0.175 | Likely Benign | -1.32 | Neutral | 0.979 | Probably Damaging | 0.973 | Probably Damaging | 2.71 | Benign | 0.04 | Affected | 0.2048 | 0.6514 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3263G>T | S1088I 2D AIThe SynGAP1 missense variant S1088I is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443815‑G‑T). 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 is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the balance of evidence, the variant is most likely benign; 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 | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | 6-33443815-G-T | -4.893 | Likely Benign | 0.891 | Likely Pathogenic | Ambiguous | 0.288 | Likely Benign | -2.05 | Neutral | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.62 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1322 | 0.5712 | -2 | -1 | 5.3 | 26.08 | ||||||||||||||||||||||||||||||||||||
| c.3264C>A | S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and is present in gnomAD (ID 6‑33443816‑C‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic versus four benign predictions—suggests the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | 6-33443816-C-A | -4.588 | Likely Benign | 0.988 | Likely Pathogenic | Likely Pathogenic | 0.181 | Likely Benign | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1190 | 0.4502 | -1 | 0 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.3264C>G | S1088R 2D AIThe SynGAP1 missense variant S1088R has no ClinVar record and is not listed 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation, with no conflict with ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.975261 | Binding | 0.336 | 0.889 | 1.000 | -4.588 | Likely Benign | 0.988 | Likely Pathogenic | Likely Pathogenic | 0.181 | Likely Benign | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1190 | 0.4502 | -1 | 0 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||||
| c.2929G>A | A977T 2D AIThe SynGAP1 missense variant A977T 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 | 0.882776 | Disordered | 0.975330 | Binding | 0.306 | 0.884 | 0.625 | -3.814 | Likely Benign | 0.118 | Likely Benign | Likely Benign | 0.106 | Likely Benign | -0.84 | Neutral | 0.965 | Probably Damaging | 0.782 | Possibly Damaging | 4.00 | Benign | 0.02 | Affected | 0.2155 | 0.6185 | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| 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.2929G>T | A977S 2D AIThe SynGAP1 missense variant A977S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign 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 indicates that A977S 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 | 0.975330 | Binding | 0.306 | 0.884 | 0.625 | -2.909 | Likely Benign | 0.089 | Likely Benign | Likely Benign | 0.091 | Likely Benign | -0.38 | Neutral | 0.965 | Probably Damaging | 0.702 | Possibly Damaging | 4.02 | Benign | 0.45 | Tolerated | 0.2820 | 0.5373 | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| 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.2930C>G | A977G 2D AIThe SynGAP1 missense variant A977G is not reported 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 A977G, 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 | 0.975330 | Binding | 0.306 | 0.884 | 0.625 | -3.250 | Likely Benign | 0.138 | Likely Benign | Likely Benign | 0.066 | Likely Benign | -0.79 | Neutral | 0.965 | Probably Damaging | 0.702 | Possibly Damaging | 4.03 | Benign | 0.05 | Affected | 0.2180 | 0.4408 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2930C>T | A977V 2D AIThe SynGAP1 missense variant A977V is not reported 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 A977V, 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 | 0.975330 | Binding | 0.306 | 0.884 | 0.625 | -3.542 | Likely Benign | 0.151 | Likely Benign | Likely Benign | 0.064 | Likely Benign | -1.15 | Neutral | 0.818 | Possibly Damaging | 0.457 | Possibly Damaging | 4.01 | Benign | 0.01 | Affected | 0.1966 | 0.5727 | 0 | 0 | 2.4 | 28.05 | |||||||||||||||||||||||||||||||||||||||
| c.2932C>A | P978T 2D AIThe SynGAP1 missense variant P978T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | -4.949 | Likely Benign | 0.217 | Likely Benign | Likely Benign | 0.125 | Likely Benign | -1.23 | Neutral | 0.818 | Possibly Damaging | 0.453 | Possibly Damaging | 4.21 | Benign | 0.04 | Affected | 0.1817 | 0.7089 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.2932C>G | P978A 2D AIThe SynGAP1 missense variant P978A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | -3.994 | Likely Benign | 0.121 | Likely Benign | Likely Benign | 0.062 | Likely Benign | -1.39 | Neutral | 0.008 | Benign | 0.010 | Benign | 4.30 | Benign | 0.07 | Tolerated | 0.3417 | 0.5891 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.2932C>T | P978S 2D AIThe SynGAP1 missense variant P978S is listed in ClinVar (ID 3379672.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a benign effect, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | Uncertain | 1 | -3.913 | Likely Benign | 0.151 | Likely Benign | Likely Benign | 0.085 | Likely Benign | -1.07 | Neutral | 0.481 | Possibly Damaging | 0.220 | Benign | 4.22 | Benign | 0.48 | Tolerated | 0.3428 | 0.6001 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||
| c.2933C>A | P978Q 2D AIThe SynGAP1 missense variant P978Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | -4.741 | Likely Benign | 0.305 | Likely Benign | Likely Benign | 0.091 | Likely Benign | -1.72 | Neutral | 0.990 | Probably Damaging | 0.726 | Possibly Damaging | 4.15 | Benign | 0.01 | Affected | 0.1651 | 0.5699 | 0 | -1 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||||||
| c.2933C>G | P978R 2D AIThe SynGAP1 missense variant P978R is not reported 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. In contrast, polyPhen‑2 (HumDiv and HumVar) 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 interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that P978R 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 | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | -2.852 | Likely Benign | 0.487 | Ambiguous | Likely Benign | 0.105 | Likely Benign | -2.10 | Neutral | 0.970 | Probably Damaging | 0.726 | Possibly Damaging | 4.15 | Benign | 0.01 | Affected | 0.1530 | 0.4590 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.2933C>T | P978L 2D AIThe SynGAP1 missense variant P978L is not reported 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 from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.975775 | Binding | 0.425 | 0.892 | 0.625 | -4.621 | Likely Benign | 0.386 | Ambiguous | Likely Benign | 0.092 | Likely Benign | -2.08 | Neutral | 0.818 | Possibly Damaging | 0.378 | Benign | 4.15 | Benign | 0.01 | Affected | 0.2326 | 0.6997 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| c.2872C>A | H958N 2D AIThe SynGAP1 missense variant H958N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -8.644 | Likely Pathogenic | 0.097 | Likely Benign | Likely Benign | 0.110 | Likely Benign | -0.56 | Neutral | 0.836 | Possibly Damaging | 0.232 | Benign | 4.17 | Benign | 1.00 | Tolerated | 0.2358 | 0.3638 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2872C>G | H958D 2D AIThe SynGAP1 missense variant H958D 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and 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 | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -11.494 | Likely Pathogenic | 0.227 | Likely Benign | Likely Benign | 0.200 | Likely Benign | -0.55 | Neutral | 0.925 | Possibly Damaging | 0.232 | Benign | 4.16 | Benign | 0.55 | Tolerated | 0.2732 | 0.2866 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2872C>T | H958Y 2D AIThe SynGAP1 missense variant H958Y 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -8.393 | Likely Pathogenic | 0.132 | Likely Benign | Likely Benign | 0.129 | Likely Benign | -1.03 | Neutral | 0.836 | Possibly Damaging | 0.232 | Benign | 4.14 | Benign | 0.06 | Tolerated | 0.1792 | 0.4706 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2873A>C | H958P 2D AIThe SynGAP1 missense variant H958P is listed in ClinVar as a benign alteration (ClinVar ID 1006798.0) and is present in the gnomAD database (gnomAD ID 6‑33443425‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 aligns with the ClinVar benign status, showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | Benign | 1 | 6-33443425-A-C | 2 | 1.24e-6 | -8.369 | Likely Pathogenic | 0.068 | Likely Benign | Likely Benign | 0.204 | Likely Benign | -0.36 | Neutral | 0.925 | Possibly Damaging | 0.316 | Benign | 4.14 | Benign | 0.10 | Tolerated | 3.77 | 5 | 0.2290 | 0.4701 | 0 | -2 | 1.6 | -40.02 | ||||||||||||||||||||||||||||||||
| c.2873A>G | H958R 2D AIThe SynGAP1 missense variant H958R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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 | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -9.188 | Likely Pathogenic | 0.169 | Likely Benign | Likely Benign | 0.134 | Likely Benign | -1.29 | Neutral | 0.836 | Possibly Damaging | 0.232 | Benign | 4.17 | Benign | 0.09 | Tolerated | 0.2440 | 0.3410 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2873A>T | H958L 2D AIThe SynGAP1 missense variant H958L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, SIFT and ESM1b, predict a pathogenic outcome. When the high‑accuracy consensus is considered, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a likely benign verdict, and AlphaMissense‑Optimized also reports benign. Foldetta predictions are unavailable. Overall, the majority of evidence supports a benign interpretation, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign and does not contradict existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -8.422 | Likely Pathogenic | 0.087 | Likely Benign | Likely Benign | 0.181 | Likely Benign | -1.28 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.25 | Benign | 0.03 | Affected | 0.1723 | 0.5338 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2874C>A | H958Q 2D AIThe SynGAP1 missense variant H958Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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 | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -8.625 | Likely Pathogenic | 0.117 | Likely Benign | Likely Benign | 0.144 | Likely Benign | -0.97 | Neutral | 0.925 | Possibly Damaging | 0.316 | Benign | 4.18 | Benign | 0.11 | Tolerated | 0.2281 | 0.3736 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2874C>G | H958Q 2D AIThe SynGAP1 missense variant H958Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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 | 0.985964 | Disordered | 0.976011 | Binding | 0.371 | 0.913 | 0.750 | -8.625 | Likely Pathogenic | 0.117 | Likely Benign | Likely Benign | 0.144 | Likely Benign | -0.97 | Neutral | 0.925 | Possibly Damaging | 0.316 | Benign | 4.18 | Benign | 0.11 | Tolerated | 0.2281 | 0.3736 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3286G>A | E1096K 2D AIThe SynGAP1 missense variant E1096K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic 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 show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -4.148 | Likely Benign | 0.845 | Likely Pathogenic | Ambiguous | 0.097 | Likely Benign | -1.44 | Neutral | 0.872 | Possibly Damaging | 0.478 | Possibly Damaging | 2.75 | Benign | 0.15 | Tolerated | 0.2440 | 0.7533 | 0 | 1 | -0.4 | -0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3286G>C | E1096Q 2D AIThe SynGAP1 missense variant E1096Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 high‑accuracy tools suggests that E1096Q 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 | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -3.134 | Likely Benign | 0.462 | Ambiguous | Likely Benign | 0.142 | Likely Benign | -1.08 | Neutral | 0.954 | Possibly Damaging | 0.654 | Possibly Damaging | 2.73 | Benign | 0.29 | Tolerated | 0.1527 | 0.7459 | 2 | 2 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3287A>C | E1096A 2D AIThe SynGAP1 missense variant E1096A is listed in ClinVar (ID 2579889.0) with an uncertain significance annotation and is not reported in gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv assigns a pathogenic label, while AlphaMissense‑Default remains uncertain. 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, has no available result for this variant. Overall, the aggregate evidence points to a benign effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | Uncertain | 1 | -4.504 | Likely Benign | 0.510 | Ambiguous | Likely Benign | 0.164 | Likely Benign | -1.37 | Neutral | 0.626 | Possibly Damaging | 0.184 | Benign | 2.77 | Benign | 0.16 | Tolerated | 3.77 | 5 | 0.3805 | 0.7569 | -1 | 0 | 5.3 | -58.04 | |||||||||||||||||||||||||||||||||||
| c.3287A>G | E1096G 2D AIThe SynGAP1 missense variant E1096G is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors shows a split: polyPhen‑2 HumDiv and HumVar classify it as pathogenic, whereas REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized predict a benign effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome, and AlphaMissense‑Optimized itself 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 high‑accuracy tools (AlphaMissense‑Optimized and SGM‑Consensus) indicate a benign impact, and no evidence contradicts this assessment with ClinVar data, which is currently lacking. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -2.749 | Likely Benign | 0.536 | Ambiguous | Likely Benign | 0.118 | Likely Benign | -2.14 | Neutral | 0.872 | Possibly Damaging | 0.478 | Possibly Damaging | 2.70 | Benign | 0.06 | Tolerated | 0.2789 | 0.6220 | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||||||
| c.3287A>T | E1096V 2D AIThe SynGAP1 missense variant E1096V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence indicates 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 | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -3.588 | Likely Benign | 0.650 | Likely Pathogenic | Likely Benign | 0.138 | Likely Benign | -1.06 | Neutral | 0.043 | Benign | 0.017 | Benign | 2.81 | Benign | 0.03 | Affected | 0.1082 | 0.7596 | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||||||
| c.3288G>C | E1096D 2D AIThe SynGAP1 missense variant E1096D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign interpretation, 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 | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -3.818 | Likely Benign | 0.192 | Likely Benign | Likely Benign | 0.116 | Likely Benign | -0.40 | Neutral | 0.115 | Benign | 0.052 | Benign | 2.71 | Benign | 0.38 | Tolerated | 0.2034 | 0.4994 | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3288G>T | E1096D 2D AIThe SynGAP1 missense variant E1096D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion is not contradicted by 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 | 0.926919 | Disordered | 0.976475 | Binding | 0.308 | 0.858 | 1.000 | -3.818 | Likely Benign | 0.192 | Likely Benign | Likely Benign | 0.116 | Likely Benign | -0.40 | Neutral | 0.115 | Benign | 0.052 | Benign | 2.71 | Benign | 0.38 | Tolerated | 0.2034 | 0.4994 | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3265G>A | G1089R 2D AIThe SynGAP1 missense variant G1089R is catalogued in gnomAD (ID 6‑33443817‑G‑A) but has no ClinVar entry. Functional prediction tools split in a 6‑to‑3 ratio: benign calls come from REVEL, polyPhen‑2 HumVar, and ESM1b, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an Uncertain result, and no Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors lean toward pathogenicity, and this assessment does not conflict with ClinVar status, which is currently unreported. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | 6-33443817-G-A | 1 | 6.35e-7 | -4.757 | Likely Benign | 0.897 | Likely Pathogenic | Ambiguous | 0.222 | Likely Benign | -3.13 | Deleterious | 0.896 | Possibly Damaging | 0.325 | Benign | 2.42 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.0934 | 0.4415 | -2 | -3 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||
| c.3265G>C | G1089R 2D AIThe SynGAP1 missense variant G1089R 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 HumVar, and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. Grouping by consensus, seven tools predict pathogenicity and three predict benign, giving a net pathogenic signal. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic. Foldetta stability analysis is unavailable. Overall, the evidence points to the variant being most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | -4.757 | Likely Benign | 0.897 | Likely Pathogenic | Ambiguous | 0.228 | Likely Benign | -3.13 | Deleterious | 0.896 | Possibly Damaging | 0.325 | Benign | 2.42 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0.0934 | 0.4415 | -2 | -3 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||||
| c.3265G>T | G1089W 2D  AIThe SynGAP1 missense variant G1089W is not reported in ClinVar and has no allele in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the consensus SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a Likely Pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no available Foldetta stability data. Overall, the majority of evidence points to a deleterious 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 | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | -6.561 | Likely Benign | 0.863 | Likely Pathogenic | Ambiguous | 0.236 | Likely Benign | -3.45 | Deleterious | 1.000 | Probably Damaging | 0.988 | Probably Damaging | 2.37 | Pathogenic | 0.00 | Affected | 0.0840 | 0.4610 | -7 | -2 | -0.5 | 129.16 | |||||||||||||||||||||||||||||||||||||||
| c.3266G>A | G1089E 2D  AIThe SynGAP1 missense variant G1089E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a 2‑vs‑2 split, 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 because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | -3.233 | Likely Benign | 0.926 | Likely Pathogenic | Ambiguous | 0.170 | Likely Benign | -2.85 | Deleterious | 0.992 | Probably Damaging | 0.834 | Possibly Damaging | 2.59 | Benign | 0.01 | Affected | 0.1460 | 0.4387 | 0 | -2 | -3.1 | 72.06 | ||||||||||||||||||||||||||||||||||||||||
| c.3266G>C | G1089A 2D AIThe SynGAP1 missense variant G1089A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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 | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | -2.864 | Likely Benign | 0.224 | Likely Benign | Likely Benign | 0.142 | Likely Benign | -1.73 | Neutral | 0.186 | Benign | 0.055 | Benign | 2.45 | Pathogenic | 0.02 | Affected | 0.3475 | 0.5331 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3266G>T | G1089V 2D AIThe SynGAP1 missense variant G1089V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for G1089V. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.891961 | Disordered | 0.976771 | Binding | 0.366 | 0.890 | 1.000 | -4.809 | Likely Benign | 0.527 | Ambiguous | Likely Benign | 0.182 | Likely Benign | -2.81 | Deleterious | 0.984 | Probably Damaging | 0.722 | Possibly Damaging | 2.40 | Pathogenic | 0.00 | Affected | 0.1326 | 0.4413 | -1 | -3 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||||||||||
| c.3256C>A | P1086T 2D AIThe SynGAP1 missense variant P1086T is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. The variant is most likely pathogenic based on the available computational evidence, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | 6-33443808-C-A | -4.181 | Likely Benign | 0.568 | Likely Pathogenic | Likely Benign | 0.229 | Likely Benign | -2.97 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.75 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1343 | 0.5848 | -1 | 0 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||
| c.3256C>G | P1086A 2D AIThe SynGAP1 missense variant P1086A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign, and Foldetta data are unavailable. Taken together, the balance of evidence points to a benign effect for P1086A. This conclusion does not conflict with 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. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | -4.317 | Likely Benign | 0.372 | Ambiguous | Likely Benign | 0.206 | Likely Benign | -2.98 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.78 | Benign | 0.00 | Affected | 0.3084 | 0.4463 | 1 | -1 | 3.4 | -26.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3256C>T | P1086S 2D AIThe SynGAP1 missense variant P1086S is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | 6-33443808-C-T | -3.165 | Likely Benign | 0.604 | Likely Pathogenic | Likely Benign | 0.212 | Likely Benign | -3.04 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.78 | Benign | 0.00 | Affected | 3.77 | 5 | 0.3067 | 0.4894 | -1 | 1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||
| c.3257C>A | P1086Q 2D AIThe SynGAP1 missense variant P1086Q is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33443809‑C‑A). 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 (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 predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | 6-33443809-C-A | -4.668 | Likely Benign | 0.652 | Likely Pathogenic | Likely Benign | 0.185 | Likely Benign | -2.92 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.77 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1285 | 0.4784 | -1 | 0 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||||
| c.3257C>G | P1086R 2D AIThe SynGAP1 missense variant P1086R is not 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 predict a pathogenic effect comprise 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 (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, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy consensus is inconclusive. Therefore, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | -5.190 | Likely Benign | 0.848 | Likely Pathogenic | Ambiguous | 0.205 | Likely Benign | -3.42 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.86 | Benign | 0.00 | Affected | 0.1319 | 0.3551 | 0 | -2 | -2.9 | 59.07 | ||||||||||||||||||||||||||||||||||||||||
| c.3257C>T | P1086L 2D AIThe SynGAP1 missense variant P1086L 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which simply indicates the variant has not yet been reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.849326 | Disordered | 0.977190 | Binding | 0.393 | 0.885 | 1.000 | -4.694 | Likely Benign | 0.607 | Likely Pathogenic | Likely Benign | 0.166 | Likely Benign | -3.57 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.73 | Benign | 0.00 | Affected | 0.2055 | 0.6326 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||||||
| 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.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.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.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.2935T>A | F979I 2D AIThe SynGAP1 missense variant F979I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods reinforce the benign prediction: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta data are missing. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -4.053 | Likely Benign | 0.512 | Ambiguous | Likely Benign | 0.163 | Likely Benign | -1.07 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 4.19 | Benign | 0.06 | Tolerated | 0.2368 | 0.3009 | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2935T>C | F979L 2D AIThe SynGAP1 missense variant F979L (ClinVar ID 1000410.0, status Uncertain, not found in gnomAD) has been evaluated by multiple in silico predictors. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while pathogenic predictions are reported by polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta, 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 status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | Uncertain | 1 | -2.341 | Likely Benign | 0.870 | Likely Pathogenic | Ambiguous | 0.228 | Likely Benign | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 0.2447 | 0.3876 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.2935T>G | F979V 2D AIThe SynGAP1 missense variant F979V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for F979V, 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 | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -3.325 | Likely Benign | 0.434 | Ambiguous | Likely Benign | 0.199 | Likely Benign | -1.03 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 4.21 | Benign | 0.04 | Affected | 0.2260 | 0.3176 | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||||||
| c.2936T>A | F979Y 2D AIThe SynGAP1 missense variant F979Y is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -3.420 | Likely Benign | 0.277 | Likely Benign | Likely Benign | 0.123 | Likely Benign | -0.26 | Neutral | 0.451 | Benign | 0.285 | Benign | 4.18 | Benign | 0.06 | Tolerated | 0.1451 | 0.2843 | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2936T>C | F979S 2D AIThe SynGAP1 missense variant F979S 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 high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and the AlphaMissense‑Optimized score also indicates a benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for F979S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -2.350 | Likely Benign | 0.718 | Likely Pathogenic | Likely Benign | 0.211 | Likely Benign | -0.05 | Neutral | 0.451 | Benign | 0.220 | Benign | 4.23 | Benign | 0.01 | Affected | 0.4397 | 0.0384 | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||||||
| c.2936T>G | F979C 2D AIThe SynGAP1 missense variant F979C is not reported in ClinVar and has no gnomAD entry. Consensus from high‑accuracy predictors is benign: AlphaMissense‑Optimized scores it benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign. Other tools that agree with benign include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, did not return a result for this variant, so its stability impact is unavailable. Overall, the majority of evidence points to a benign effect, 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 | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -6.395 | Likely Benign | 0.589 | Likely Pathogenic | Likely Benign | 0.160 | Likely Benign | -0.94 | Neutral | 0.994 | Probably Damaging | 0.888 | Possibly Damaging | 4.15 | Benign | 0.00 | Affected | 0.2646 | 0.2179 | -4 | -2 | -0.3 | -44.04 | |||||||||||||||||||||||||||||||||||||||
| c.2937C>A | F979L 2D AIThe SynGAP1 missense variant F979L has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -2.341 | Likely Benign | 0.870 | Likely Pathogenic | Ambiguous | 0.328 | Likely Benign | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 0.2447 | 0.3876 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||
| c.2937C>G | F979L 2D AIThe SynGAP1 missense variant F979L has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.816150 | Disordered | 0.977500 | Binding | 0.274 | 0.889 | 0.625 | -2.341 | Likely Benign | 0.870 | Likely Pathogenic | Ambiguous | 0.328 | Likely Benign | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 0.2447 | 0.3876 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||
| c.4015A>C | N1339H 2D AIThe SynGAP1 missense variant N1339H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and 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 outcome: AlphaMissense‑Optimized predicts benign, SGM‑Consensus likewise indicates likely benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -3.487 | Likely Benign | 0.338 | Likely Benign | Likely Benign | 0.234 | Likely Benign | -2.98 | Deleterious | 0.994 | Probably Damaging | 0.987 | Probably Damaging | 2.87 | Benign | 0.00 | Affected | 0.1585 | 0.7644 | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||||||
| c.4015A>G | N1339D 2D AIThe SynGAP1 missense variant N1339D is catalogued in gnomAD (ID 6‑33451889‑A‑G) but has no ClinVar submission. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. When aggregated into a consensus, the four contributing scores (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) split evenly, leaving the SGM Consensus inconclusive. High‑accuracy assessments further indicate a benign outcome from AlphaMissense‑Optimized; the SGM Consensus and Foldetta predictions are unavailable. Overall, the majority of individual tools predict pathogenicity, and the high‑accuracy benign prediction does 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. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | 6-33451889-A-G | -2.533 | Likely Benign | 0.634 | Likely Pathogenic | Likely Benign | 0.186 | Likely Benign | -3.04 | Deleterious | 0.980 | Probably Damaging | 0.956 | Probably Damaging | 2.92 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2087 | 0.4721 | 1 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||
| c.4015A>T | N1339Y 2D AIThe SynGAP1 missense variant N1339Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta data are unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the variant’s impact uncertain. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -3.808 | Likely Benign | 0.578 | Likely Pathogenic | Likely Benign | 0.319 | Likely Benign | -4.83 | Deleterious | 0.994 | Probably Damaging | 0.990 | Probably Damaging | 2.87 | Benign | 0.00 | Affected | 0.0697 | 0.6573 | -2 | -2 | 2.2 | 49.07 | ||||||||||||||||||||||||||||||||||||||||
| c.4016A>C | N1339T 2D AIThe SynGAP1 missense variant N1339T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta results are unavailable. Based on the most reliable 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. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -2.682 | Likely Benign | 0.448 | Ambiguous | Likely Benign | 0.251 | Likely Benign | -3.31 | Deleterious | 0.980 | Probably Damaging | 0.956 | Probably Damaging | 2.89 | Benign | 0.00 | Affected | 0.1443 | 0.7598 | 0 | 0 | 2.8 | -13.00 | ||||||||||||||||||||||||||||||||||||||||
| c.4016A>G | N1339S 2D AIThe SynGAP1 missense variant N1339S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (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 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 | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -2.331 | Likely Benign | 0.197 | Likely Benign | Likely Benign | 0.178 | Likely Benign | -2.66 | Deleterious | 0.980 | Probably Damaging | 0.935 | Probably Damaging | 2.91 | Benign | 0.00 | Affected | 0.3735 | 0.7283 | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||||||
| c.4016A>T | N1339I 2D AIThe SynGAP1 missense variant N1339I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 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 predictions (five pathogenic vs four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic based on current computational evidence, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -3.104 | Likely Benign | 0.740 | Likely Pathogenic | Likely Benign | 0.306 | Likely Benign | -5.25 | Deleterious | 0.994 | Probably Damaging | 0.987 | Probably Damaging | 2.87 | Benign | 0.00 | Affected | 0.0747 | 0.6271 | -2 | -3 | 8.0 | -0.94 | ||||||||||||||||||||||||||||||||||||||||
| c.4017C>A | N1339K 2D AIThe SynGAP1 missense variant N1339K is listed in gnomAD (ID 6‑33451891‑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 returns an uncertain result. The high‑accuracy consensus (SGM Consensus) – a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method, has no reported output for this variant. Overall, the majority of available tools (five pathogenic vs. three benign) predict a deleterious effect. The variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | 6-33451891-C-A | -3.009 | Likely Benign | 0.872 | Likely Pathogenic | Ambiguous | 0.169 | Likely Benign | -3.56 | Deleterious | 0.980 | Probably Damaging | 0.968 | Probably Damaging | 2.90 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2201 | 0.6507 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||
| c.4017C>G | N1339K 2D AISynGAP1 missense variant N1339K is not reported in ClinVar and is absent from gnomAD. 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 (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑to‑2 tie, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.771762 | Disordered | 0.977585 | Binding | 0.396 | 0.687 | 1.000 | -3.009 | Likely Benign | 0.872 | Likely Pathogenic | Ambiguous | 0.181 | Likely Benign | -3.56 | Deleterious | 0.980 | Probably Damaging | 0.968 | Probably Damaging | 2.90 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2201 | 0.6507 | 0 | 1 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||||||||||
| c.4018A>C | T1340P 2D AIThe SynGAP1 missense variant T1340P is catalogued in gnomAD (ID 6‑33451892‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while only SIFT predicts 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 this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that T1340P 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 | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | 6-33451892-A-C | -2.681 | Likely Benign | 0.102 | Likely Benign | Likely Benign | 0.190 | Likely Benign | -1.81 | Neutral | 0.334 | Benign | 0.099 | Benign | 4.08 | Benign | 0.01 | Affected | 3.77 | 5 | 0.2268 | 0.4983 | -1 | 0 | -0.9 | -3.99 | ||||||||||||||||||||||||||||||||||||
| c.4018A>G | T1340A 2D AIThe SynGAP1 missense variant T1340A 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, 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 unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, supports a benign classification. 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 | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | -3.192 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.116 | Likely Benign | -1.01 | Neutral | 0.010 | Benign | 0.011 | Benign | 4.20 | Benign | 0.02 | Affected | 0.3984 | 0.4288 | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||||||
| c.4018A>T | T1340S 2D AIThe SynGAP1 missense variant T1340S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | -2.698 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.116 | Likely Benign | 0.62 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.87 | Benign | 1.00 | Tolerated | 0.3436 | 0.4521 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.4019C>A | T1340N 2D AIThe SynGAP1 missense variant T1340N is reported in gnomAD (ID 6‑33451893‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for T1340N. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | 6-33451893-C-A | -3.664 | Likely Benign | 0.154 | Likely Benign | Likely Benign | 0.071 | Likely Benign | -0.95 | Neutral | 0.092 | Benign | 0.026 | Benign | 4.09 | Benign | 0.02 | Affected | 3.77 | 5 | 0.1755 | 0.5309 | 0 | 0 | -2.8 | 13.00 | ||||||||||||||||||||||||||||||||||||
| c.4019C>G | T1340S 2D AIThe SynGAP1 missense variant T1340S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | -2.698 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.083 | Likely Benign | 0.62 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.87 | Benign | 1.00 | Tolerated | 0.3436 | 0.4521 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.4019C>T | T1340I 2D AIThe SynGAP1 missense variant T1340I is not reported in ClinVar (ClinVar status: “None”) but is present in gnomAD (ID 6‑33451893‑C‑T). 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 and SIFT. AlphaMissense‑Default is uncertain, while AlphaMissense‑Optimized predicts benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (two benign versus one pathogenic, with the uncertain result treated as unavailable). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the high‑accuracy predictions (AlphaMissense‑Optimized, SGM Consensus) both indicate a benign impact, and no evidence contradicts this assessment with the ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.977899 | Binding | 0.444 | 0.697 | 0.750 | 6-33451893-C-T | -3.476 | Likely Benign | 0.402 | Ambiguous | Likely Benign | 0.089 | Likely Benign | -2.57 | Deleterious | 0.334 | Benign | 0.099 | Benign | 4.08 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1163 | 0.5848 | -1 | 0 | 5.2 | 12.05 | |||||||||||||||||||||||||||||||||||||
| c.2773C>A | L925I 2D  AIThe SynGAP1 missense variant L925I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) lean toward a pathogenic interpretation. This prediction does not contradict ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -5.266 | Likely Benign | 0.828 | Likely Pathogenic | Ambiguous | 0.205 | Likely Benign | -1.38 | Neutral | 0.999 | Probably Damaging | 0.994 | Probably Damaging | 1.37 | Pathogenic | 0.00 | Affected | 0.1192 | 0.3405 | 2 | 2 | 0.7 | 0.00 | ||||||||||||||||||||||||||||||||||||||||
| c.2773C>G | L925V 2D AIThe SynGAP1 missense variant L925V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and this prediction does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -3.977 | Likely Benign | 0.831 | Likely Pathogenic | Ambiguous | 0.244 | Likely Benign | -2.09 | Neutral | 0.999 | Probably Damaging | 0.994 | Probably Damaging | 1.36 | Pathogenic | 0.00 | Affected | 0.1848 | 0.3230 | 2 | 1 | 0.4 | -14.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2773C>T | L925F 2D  AIThe SynGAP1 missense variant L925F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic impact for the L925F substitution, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -4.147 | Likely Benign | 0.966 | Likely Pathogenic | Likely Pathogenic | 0.242 | Likely Benign | -3.04 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 1.32 | Pathogenic | 0.00 | Affected | 0.0897 | 0.2881 | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2774T>A | L925H 2D  AIThe SynGAP1 missense variant L925H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability result is available. Overall, the majority of evidence points to a pathogenic effect for L925H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -3.369 | Likely Benign | 0.997 | Likely Pathogenic | Likely Pathogenic | 0.475 | Likely Benign | -5.24 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.28 | Pathogenic | 0.00 | Affected | 0.1219 | 0.1494 | -2 | -3 | -7.0 | 23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2774T>C | L925P 2D AIThe SynGAP1 missense variant L925P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that 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 | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -2.733 | Likely Benign | 0.985 | Likely Pathogenic | Likely Pathogenic | 0.501 | Likely Pathogenic | -5.12 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.28 | Pathogenic | 0.00 | Affected | 0.3083 | 0.1996 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||||||
| c.2774T>G | L925R 2D AIThe SynGAP1 missense variant L925R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus indicates a likely pathogenic classification. Foldetta results are not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.483068 | Structured | 0.977963 | Binding | 0.290 | 0.852 | 0.125 | -2.340 | Likely Benign | 0.984 | Likely Pathogenic | Likely Pathogenic | 0.519 | Likely Pathogenic | -4.54 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.28 | Pathogenic | 0.00 | Affected | 0.1278 | 0.1294 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.2893C>A | H965N 2D AIThe SynGAP1 missense variant H965N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Across the available in‑silico predictors, the majority (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a benign effect, while no tool predicts pathogenicity. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -7.605 | In-Between | 0.082 | Likely Benign | Likely Benign | 0.076 | Likely Benign | -0.50 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.09 | Benign | 0.80 | Tolerated | 0.2360 | 0.3838 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2893C>G | H965D 2D AIThe SynGAP1 missense variant H965D is reported in gnomAD (6‑33443445‑C‑G) and has no ClinVar entry. Consensus from most in silico predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classifies the change as benign, while only the ESM1b model flags it as pathogenic. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized returns a benign score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this residue, so its status is unavailable. Overall, the preponderance of evidence indicates that H965D is most likely benign, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | 6-33443445-C-G | 1 | 6.20e-7 | -9.827 | Likely Pathogenic | 0.192 | Likely Benign | Likely Benign | 0.147 | Likely Benign | -0.94 | Neutral | 0.007 | Benign | 0.018 | Benign | 4.09 | Benign | 0.62 | Tolerated | 3.77 | 5 | 0.2697 | 0.3066 | -1 | 1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||||||
| c.2893C>T | H965Y 2D AIThe SynGAP1 missense variant H965Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. The consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No tool predicts pathogenicity, and the single uncertain result from ESM1b does not alter the overall benign consensus. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta data are unavailable. Consequently, the variant is most likely benign, 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 | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -7.121 | In-Between | 0.133 | Likely Benign | Likely Benign | 0.092 | Likely Benign | -1.02 | Neutral | 0.327 | Benign | 0.147 | Benign | 4.03 | Benign | 0.25 | Tolerated | 0.1582 | 0.4906 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2894A>C | H965P 2D AIThe SynGAP1 missense variant H965P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool predicts pathogenicity. The high‑accuracy consensus methods also support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this prediction 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 | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -6.835 | Likely Benign | 0.059 | Likely Benign | Likely Benign | 0.245 | Likely Benign | -0.69 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.06 | Benign | 0.19 | Tolerated | 0.2342 | 0.4901 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2894A>G | H965R 2D AIThe SynGAP1 missense variant H965R is catalogued in gnomAD (ID 6‑33443446‑A‑G) 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, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. No tool predicts pathogenicity; ESM1b is uncertain but does not contradict the benign consensus. High‑accuracy assessments confirm this view: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus likewise indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so it does not influence the assessment. Overall, the available predictions strongly suggest that H965R 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 | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | 6-33443446-A-G | 1 | 6.20e-7 | -7.056 | In-Between | 0.156 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -0.88 | Neutral | 0.065 | Benign | 0.049 | Benign | 4.08 | Benign | 0.38 | Tolerated | 3.77 | 5 | 0.2394 | 0.3610 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||||
| c.2894A>T | H965L 2D AIThe SynGAP1 missense variant H965L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect. Benign predictors include REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool in the dataset returned a pathogenic prediction. Consensus predictors such as SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classify the variant as Likely Benign. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus is Likely Benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -6.708 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.128 | Likely Benign | -1.66 | Neutral | 0.033 | Benign | 0.018 | Benign | 4.06 | Benign | 1.00 | Tolerated | 0.1606 | 0.5338 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2895C>A | H965Q 2D AIThe SynGAP1 missense variant H965Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -6.447 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.042 | Likely Benign | -0.71 | Neutral | 0.138 | Benign | 0.105 | Benign | 4.09 | Benign | 0.28 | Tolerated | 0.2257 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2895C>G | H965Q 2D AIThe SynGAP1 missense variant H965Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect. Consensus predictors such as SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classify the variant as Likely Benign. Individual algorithms—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—all predict a benign outcome. No tool in the dataset returned a pathogenic prediction. High‑accuracy methods: AlphaMissense‑Optimized is benign; SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.988505 | Disordered | 0.978700 | Binding | 0.342 | 0.882 | 0.750 | -6.447 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.043 | Likely Benign | -0.71 | Neutral | 0.138 | Benign | 0.105 | Benign | 4.09 | Benign | 0.28 | Tolerated | 0.2257 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3253C>G | R1085G 2D AIThe SynGAP1 missense variant R1085G is reported in gnomAD (ID 6‑33443805‑C‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, ESM1b, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a 2‑to‑2 split, leaving the consensus inconclusive. No Foldetta stability assessment is available. Overall, the majority of evidence (five pathogenic versus three benign) points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.978838 | Binding | 0.270 | 0.888 | 1.000 | 6-33443805-C-G | -4.225 | Likely Benign | 0.846 | Likely Pathogenic | Ambiguous | 0.179 | Likely Benign | -2.79 | Deleterious | 0.997 | Probably Damaging | 0.993 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | 0.3310 | 0.3693 | -2 | -3 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||||||||
| c.3253C>T | R1085W 2D AISynGAP1 missense variant R1085W is listed in ClinVar as Uncertain and is present in gnomAD (ID 6‑33443805‑C‑T). Prediction tools that classify the variant as benign include REVEL, ESM1b, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, which contradicts the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.978838 | Binding | 0.270 | 0.888 | 1.000 | Uncertain | 1 | 6-33443805-C-T | 2 | 1.26e-6 | -6.339 | Likely Benign | 0.821 | Likely Pathogenic | Ambiguous | 0.202 | Likely Benign | -3.15 | Deleterious | 1.000 | Probably Damaging | 0.996 | Probably Damaging | 2.70 | Benign | 0.00 | Affected | 3.77 | 5 | 0.1238 | 0.3700 | -3 | 2 | 3.6 | 30.03 | |||||||||||||||||||||||||||||||||
| c.3254G>A | R1085Q 2D AIThe SynGAP1 missense variant R1085Q (ClinVar ID 1729448.0) is listed as ClinVar status Uncertain and is present in gnomAD (6‑33443806‑G‑A). Functional prediction tools show a split opinion: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic predictions are reported by 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 interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also favors benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, which is consistent with the ClinVar uncertain designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.978838 | Binding | 0.270 | 0.888 | 1.000 | Uncertain | 1 | 6-33443806-G-A | 5 | 3.16e-6 | -3.843 | Likely Benign | 0.589 | Likely Pathogenic | Likely Benign | 0.224 | Likely Benign | -1.43 | Neutral | 0.998 | Probably Damaging | 0.988 | Probably Damaging | 2.73 | Benign | 0.02 | Affected | 3.77 | 5 | 0.2962 | 0.2751 | 1 | 1 | 1.0 | -28.06 | ||||||||||||||||||||||||||||||||
| c.3254G>C | R1085P 2D AIThe SynGAP1 missense variant R1085P is not 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 vs 2). Foldetta results are unavailable. Overall, the majority of standard predictors (five pathogenic vs. four benign) lean toward a pathogenic interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction and the inconclusive SGM Consensus temper this view. The variant is most likely pathogenic based on the prevailing 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. | 0.852992 | Disordered | 0.978838 | Binding | 0.270 | 0.888 | 1.000 | -2.527 | Likely Benign | 0.759 | Likely Pathogenic | Likely Benign | 0.260 | Likely Benign | -2.55 | Deleterious | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.71 | Benign | 0.01 | Affected | 0.1988 | 0.4524 | 0 | -2 | 2.9 | -59.07 | ||||||||||||||||||||||||||||||||||||||||
| c.3254G>T | R1085L 2D AIThe SynGAP1 missense variant R1085L is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R1085L, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.978838 | Binding | 0.270 | 0.888 | 1.000 | -3.674 | Likely Benign | 0.734 | Likely Pathogenic | Likely Benign | 0.243 | Likely Benign | -2.38 | Neutral | 0.997 | Probably Damaging | 0.993 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 0.1909 | 0.4568 | -3 | -2 | 8.3 | -43.03 | |||||||||||||||||||||||||||||||||||||||
| c.3247A>C | K1083Q 2D  AIThe SynGAP1 missense variant K1083Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv and HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a benign impact for K1083Q, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -2.214 | Likely Benign | 0.390 | Ambiguous | Likely Benign | 0.099 | Likely Benign | -0.50 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 4.06 | Benign | 0.37 | Tolerated | 0.4821 | 0.1647 | 1 | 1 | 0.4 | -0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3247A>G | K1083E 2D  AIThe SynGAP1 missense variant K1083E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -3.538 | Likely Benign | 0.864 | Likely Pathogenic | Ambiguous | 0.133 | Likely Benign | -0.78 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 4.09 | Benign | 0.27 | Tolerated | 0.4135 | 0.1717 | 0 | 1 | 0.4 | 0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3248A>C | K1083T 2D  AIThe SynGAP1 missense variant K1083T is reported in gnomAD (ID 6‑33443800‑A‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; 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 is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | 6-33443800-A-C | 2 | 1.26e-6 | -2.870 | Likely Benign | 0.690 | Likely Pathogenic | Likely Benign | 0.233 | Likely Benign | -0.76 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 4.05 | Benign | 0.31 | Tolerated | 3.77 | 5 | 0.2192 | 0.4150 | -1 | 0 | 3.2 | -27.07 | ||||||||||||||||||||||||||||||||||
| c.3248A>G | K1083R 2D  AIThe SynGAP1 missense variant K1083R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this 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 | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -2.212 | Likely Benign | 0.132 | Likely Benign | Likely Benign | 0.119 | Likely Benign | -0.53 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 4.06 | Benign | 0.84 | Tolerated | 0.5053 | 0.1903 | Weaken | 3 | 2 | -0.6 | 28.01 | ||||||||||||||||||||||||||||||||||||||
| c.3248A>T | K1083I 2D  AIThe SynGAP1 missense variant K1083I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and the Foldetta stability analysis 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 | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -3.207 | Likely Benign | 0.836 | Likely Pathogenic | Ambiguous | 0.239 | Likely Benign | -1.65 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 4.02 | Benign | 0.30 | Tolerated | 0.1394 | 0.3978 | -2 | -3 | 8.4 | -15.01 | |||||||||||||||||||||||||||||||||||||||
| c.3249A>C | K1083N 2D  AIThe SynGAP1 missense variant K1083N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -4.088 | Likely Benign | 0.873 | Likely Pathogenic | Ambiguous | 0.053 | Likely Benign | -0.83 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 4.04 | Benign | 0.21 | Tolerated | 0.3939 | 0.2234 | 1 | 0 | 0.4 | -14.07 | |||||||||||||||||||||||||||||||||||||||
| c.3249A>T | K1083N 2D AIThe SynGAP1 missense variant K1083N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.837511 | Disordered | 0.978906 | Binding | 0.302 | 0.893 | 1.000 | -4.088 | Likely Benign | 0.873 | Likely Pathogenic | Ambiguous | 0.053 | Likely Benign | -0.83 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 4.04 | Benign | 0.21 | Tolerated | 0.3939 | 0.2234 | 1 | 0 | 0.4 | -14.07 | |||||||||||||||||||||||||||||||||||||||
| c.3250C>A | P1084T 2D AIThe SynGAP1 missense variant P1084T is reported in ClinVar as “Not submitted” and is present in gnomAD (ID 6‑33443802‑C‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.842060 | Disordered | 0.979020 | Binding | 0.348 | 0.889 | 1.000 | 6-33443802-C-A | -4.665 | Likely Benign | 0.089 | Likely Benign | Likely Benign | 0.127 | Likely Benign | -2.14 | Neutral | 0.025 | Benign | 0.012 | Benign | 4.11 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1546 | 0.6793 | -1 | 0 | 0.9 | 3.99 | ||||||||||||||||||||||||||||||||||||
| c.3250C>G | P1084A 2D AIThe SynGAP1 missense variant P1084A is listed in ClinVar (ID 2827308.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which itself is “Likely Benign”). In contrast, PROVEAN and polyPhen‑2 HumDiv predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, 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 | 0.842060 | Disordered | 0.979020 | Binding | 0.348 | 0.889 | 1.000 | Uncertain | 1 | -3.928 | Likely Benign | 0.066 | Likely Benign | Likely Benign | 0.114 | Likely Benign | -2.54 | Deleterious | 0.649 | Possibly Damaging | 0.157 | Benign | 4.05 | Benign | 0.35 | Tolerated | 3.77 | 5 | 0.3164 | 0.5784 | -1 | 1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.3250C>T | P1084S 2D AIThe SynGAP1 missense variant P1084S is reported in gnomAD (variant ID 6‑33443802‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.842060 | Disordered | 0.979020 | Binding | 0.348 | 0.889 | 1.000 | 6-33443802-C-T | 1 | 6.31e-7 | -3.987 | Likely Benign | 0.119 | Likely Benign | Likely Benign | 0.086 | Likely Benign | -2.24 | Neutral | 0.481 | Possibly Damaging | 0.157 | Benign | 4.03 | Benign | 0.03 | Affected | 3.77 | 5 | 0.3102 | 0.6215 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||||||
| c.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.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.3251C>T | P1084L 2D AIThe SynGAP1 missense variant P1084L is reported in gnomAD (ID 6‑33443803‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and SIFT. 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) also indicates 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). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.842060 | Disordered | 0.979020 | Binding | 0.348 | 0.889 | 1.000 | 6-33443803-C-T | 1 | 6.31e-7 | -4.547 | Likely Benign | 0.175 | Likely Benign | Likely Benign | 0.124 | Likely Benign | -3.33 | Deleterious | 0.649 | Possibly Damaging | 0.157 | Benign | 4.00 | Benign | 0.01 | Affected | 3.77 | 5 | 0.2218 | 0.6470 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||
| c.3115A>C | I1039L 2D AIThe SynGAP1 missense variant I1039L is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports 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, is not available for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -2.035 | Likely Benign | 0.269 | Likely Benign | Likely Benign | 0.083 | Likely Benign | -0.14 | Neutral | 0.264 | Benign | 0.048 | Benign | 2.82 | Benign | 0.98 | Tolerated | 0.1057 | 0.4605 | 2 | 2 | -0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.3115A>G | I1039V 2D AIThe SynGAP1 missense variant I1039V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -2.455 | Likely Benign | 0.164 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.21 | Neutral | 0.264 | Benign | 0.048 | Benign | 2.76 | Benign | 0.41 | Tolerated | 0.1405 | 0.4112 | 4 | 3 | -0.3 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3115A>T | I1039F 2D AIThe SynGAP1 missense variant I1039F is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign interpretation: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) indicate pathogenic. When predictions are grouped by agreement, the benign‑oriented tools outnumber the pathogenic ones, and the single uncertain call from AlphaMissense‑Default does not alter this balance. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. Foldetta data are unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -2.872 | Likely Benign | 0.545 | Ambiguous | Likely Benign | 0.124 | Likely Benign | -1.16 | Neutral | 0.925 | Possibly Damaging | 0.510 | Possibly Damaging | 2.68 | Benign | 0.13 | Tolerated | 0.0710 | 0.4368 | 1 | 0 | -1.7 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.3116T>A | I1039N 2D AIThe SynGAP1 missense variant I1039N 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. Tools 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 a likely benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none is present). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -3.469 | Likely Benign | 0.951 | Likely Pathogenic | Ambiguous | 0.155 | Likely Benign | -1.24 | Neutral | 0.011 | Benign | 0.010 | Benign | 2.67 | Benign | 0.02 | Affected | 0.1151 | 0.1311 | -2 | -3 | -8.0 | 0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3116T>C | I1039T 2D AIThe SynGAP1 missense variant I1039T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443668‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign outcome. Only AlphaMissense‑Default predicts a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | Uncertain | 2 | 6-33443668-T-C | 12 | 7.43e-6 | -2.465 | Likely Benign | 0.645 | Likely Pathogenic | Likely Benign | 0.193 | Likely Benign | 0.45 | Neutral | 0.004 | Benign | 0.008 | Benign | 2.75 | Benign | 0.10 | Tolerated | 3.77 | 5 | 0.1248 | 0.2293 | -1 | 0 | -5.2 | -12.05 | ||||||||||||||||||||||||||||||||
| c.3116T>G | I1039S 2D AIThe SynGAP1 missense variant I1039S 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 the substitution as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. No Foldetta stability assessment is available. 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 | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -1.688 | Likely Benign | 0.829 | Likely Pathogenic | Ambiguous | 0.171 | Likely Benign | -0.20 | Neutral | 0.032 | Benign | 0.008 | Benign | 2.76 | Benign | 0.03 | Affected | 0.2917 | 0.1294 | -1 | -2 | -5.3 | -26.08 | |||||||||||||||||||||||||||||||||||||||
| c.3117T>G | I1039M 2D AIThe SynGAP1 missense variant I1039M 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) which classifies the variant as Likely Benign. In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. 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, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for I1039M, 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 | 0.969315 | Disordered | 0.979204 | Binding | 0.292 | 0.806 | 0.625 | -3.444 | Likely Benign | 0.292 | Likely Benign | Likely Benign | 0.116 | Likely Benign | -0.38 | Neutral | 0.977 | Probably Damaging | 0.721 | Possibly Damaging | 2.68 | Benign | 0.16 | Tolerated | 0.0926 | 0.4392 | 2 | 1 | -2.6 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3283C>A | P1095T 2D AIThe SynGAP1 missense variant P1095T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | -4.706 | Likely Benign | 0.195 | Likely Benign | Likely Benign | 0.108 | Likely Benign | -1.42 | Neutral | 0.872 | Possibly Damaging | 0.399 | Benign | 2.77 | Benign | 0.13 | Tolerated | 0.1685 | 0.6677 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3283C>G | P1095A 2D AIThe SynGAP1 missense variant P1095A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | -4.555 | Likely Benign | 0.129 | Likely Benign | Likely Benign | 0.060 | Likely Benign | -0.80 | Neutral | 0.580 | Possibly Damaging | 0.242 | Benign | 2.79 | Benign | 0.18 | Tolerated | 0.3122 | 0.5703 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3283C>T | P1095S 2D AIThe SynGAP1 missense variant P1095S is reported in gnomAD (ID 6‑33443835‑C‑T) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the unanimous benign predictions and the absence of any pathogenic signal, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | 6-33443835-C-T | 7 | 4.51e-6 | -3.819 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.128 | Likely Benign | -0.64 | Neutral | 0.207 | Benign | 0.072 | Benign | 2.80 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0.3150 | 0.5963 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||||||
| c.3284C>A | P1095Q 2D AIThe SynGAP1 missense variant P1095Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | -4.171 | Likely Benign | 0.295 | Likely Benign | Likely Benign | 0.110 | Likely Benign | -1.64 | Neutral | 0.922 | Possibly Damaging | 0.441 | Benign | 2.85 | Benign | 0.45 | Tolerated | 0.1573 | 0.5519 | 0 | -1 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3284C>G | P1095R 2D AIThe SynGAP1 missense variant P1095R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which classify the change as benign or tolerant. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy consensus methods reinforce the benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and Foldetta data are missing. Overall, the majority of reliable predictors and consensus analyses indicate that P1095R is most likely benign, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | -5.180 | Likely Benign | 0.553 | Ambiguous | Likely Benign | 0.091 | Likely Benign | -1.93 | Neutral | 0.922 | Possibly Damaging | 0.528 | Possibly Damaging | 2.77 | Benign | 0.04 | Affected | 0.1513 | 0.4576 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3284C>T | P1095L 2D AIThe SynGAP1 missense variant P1095L is catalogued in gnomAD (ID 6‑33443836‑C‑T) but has no ClinVar record. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.922952 | Disordered | 0.979251 | Binding | 0.387 | 0.870 | 1.000 | 6-33443836-C-T | 1 | 6.44e-7 | -4.697 | Likely Benign | 0.363 | Ambiguous | Likely Benign | 0.126 | Likely Benign | -2.78 | Deleterious | 0.960 | Probably Damaging | 0.604 | Possibly Damaging | 2.74 | Benign | 0.03 | Affected | 3.77 | 5 | 0.2199 | 0.6347 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||
| c.4009T>A | F1337I 2D AIThe SynGAP1 missense variant F1337I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, 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 (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate a pathogenic effect. This prediction 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. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -2.761 | Likely Benign | 0.982 | Likely Pathogenic | Likely Pathogenic | 0.252 | Likely Benign | -3.32 | Deleterious | 0.947 | Possibly Damaging | 0.950 | Probably Damaging | 2.77 | Benign | 0.00 | Affected | 0.2574 | 0.2875 | 1 | 0 | 1.7 | -34.02 | ||||||||||||||||||||||||||||||||||||||||
| c.4009T>C | F1337L 2D AIThe SynGAP1 missense variant F1337L 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. 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, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a likely 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. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -2.396 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.186 | Likely Benign | -3.17 | Deleterious | 0.880 | Possibly Damaging | 0.899 | Possibly Damaging | 2.81 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2765 | 0.3543 | 0 | 2 | 1.0 | -34.02 | ||||||||||||||||||||||||||||||||||||||
| c.4009T>G | F1337V 2D AIThe SynGAP1 missense variant F1337V is not 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, and PROVEAN) is inconclusive (two pathogenic vs two benign), and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs three benign) points to a pathogenic impact. The variant is most likely pathogenic, 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. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -2.425 | Likely Benign | 0.990 | Likely Pathogenic | Likely Pathogenic | 0.335 | Likely Benign | -3.94 | Deleterious | 0.947 | Possibly Damaging | 0.932 | Probably Damaging | 2.76 | Benign | 0.00 | Affected | 0.2470 | 0.2902 | -1 | -1 | 1.4 | -48.04 | ||||||||||||||||||||||||||||||||||||||||
| c.4010T>A | F1337Y 2D AIThe SynGAP1 missense variant F1337Y is not reported 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 as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence, including the SGM‑Consensus and the majority of individual predictors, leans toward a benign interpretation. 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 | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -3.481 | Likely Benign | 0.855 | Likely Pathogenic | Ambiguous | 0.202 | Likely Benign | -1.80 | Neutral | 0.947 | Possibly Damaging | 0.899 | Possibly Damaging | 2.82 | Benign | 0.00 | Affected | 0.1722 | 0.2754 | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.4010T>C | F1337S 2D AIThe SynGAP1 missense variant F1337S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -2.641 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.327 | Likely Benign | -4.65 | Deleterious | 0.984 | Probably Damaging | 0.969 | Probably Damaging | 2.74 | Benign | 0.00 | Affected | 0.4478 | 0.0743 | -3 | -2 | -3.6 | -60.10 | ||||||||||||||||||||||||||||||||||||||||
| c.4010T>G | F1337C 2D AIThe SynGAP1 missense variant F1337C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -4.628 | Likely Benign | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.357 | Likely Benign | -4.57 | Deleterious | 0.996 | Probably Damaging | 0.984 | Probably Damaging | 2.73 | Benign | 0.00 | Affected | 0.2619 | 0.1905 | -4 | -2 | -0.3 | -44.04 | ||||||||||||||||||||||||||||||||||||||||
| c.4011C>A | F1337L 2D AIThe SynGAP1 missense variant F1337L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451885‑C‑A). 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, 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 tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. 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. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | 6-33451885-C-A | -2.396 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.111 | Likely Benign | -3.17 | Deleterious | 0.880 | Possibly Damaging | 0.899 | Possibly Damaging | 2.81 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2765 | 0.3543 | 0 | 2 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||
| c.4011C>G | F1337L 2D AIThe SynGAP1 missense variant F1337L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta data are unavailable. With a predominance of pathogenic calls and a single high‑confidence pathogenic prediction, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for F1337L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.823549 | Disordered | 0.979265 | Binding | 0.388 | 0.712 | 0.625 | -2.396 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.122 | Likely Benign | -3.17 | Deleterious | 0.880 | Possibly Damaging | 0.899 | Possibly Damaging | 2.81 | Benign | 0.00 | Affected | 3.77 | 5 | 0.2765 | 0.3543 | 0 | 2 | 1.0 | -34.02 | ||||||||||||||||||||||||||||||||||||||
| c.3244C>A | Q1082K 2D  AIThe SynGAP1 missense variant Q1082K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score benign, and AlphaMissense‑Optimized also predicts benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. No tools predict pathogenicity, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, while Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | -4.488 | Likely Benign | 0.460 | Ambiguous | Likely Benign | 0.087 | Likely Benign | -1.13 | Neutral | 0.224 | Benign | 0.058 | Benign | 4.19 | Benign | 0.12 | Tolerated | 0.2008 | 0.4972 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3244C>G | Q1082E 2D  AIThe SynGAP1 missense variant Q1082E is reported in gnomAD (ID 6‑33443796‑C‑G) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the unanimous benign predictions and lack of ClinVar pathogenic annotation, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | 6-33443796-C-G | -3.437 | Likely Benign | 0.267 | Likely Benign | Likely Benign | 0.090 | Likely Benign | -0.87 | Neutral | 0.112 | Benign | 0.026 | Benign | 4.19 | Benign | 0.07 | Tolerated | 3.77 | 5 | 0.1485 | 0.3227 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||||||||
| c.3245A>C | Q1082P 2D  AIThe SynGAP1 missense variant Q1082P is not reported 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 | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | -2.141 | Likely Benign | 0.064 | Likely Benign | Likely Benign | 0.287 | Likely Benign | -0.71 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.16 | Benign | 0.05 | Affected | 0.2121 | 0.6144 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3245A>G | Q1082R 2D  AIThe SynGAP1 missense variant Q1082R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that 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 | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | -3.584 | Likely Benign | 0.418 | Ambiguous | Likely Benign | 0.076 | Likely Benign | -0.96 | Neutral | 0.224 | Benign | 0.058 | Benign | 4.14 | Benign | 0.10 | Tolerated | 0.1590 | 0.3014 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3245A>T | Q1082L 2D  AIThe SynGAP1 missense variant Q1082L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | -3.284 | Likely Benign | 0.171 | Likely Benign | Likely Benign | 0.097 | Likely Benign | -1.30 | Neutral | 0.224 | Benign | 0.058 | Benign | 4.12 | Benign | 1.00 | Tolerated | 0.0979 | 0.6824 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3246G>C | Q1082H 2D  AIThe SynGAP1 missense variant Q1082H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | -4.307 | Likely Benign | 0.273 | Likely Benign | Likely Benign | 0.092 | Likely Benign | -1.27 | Neutral | 0.002 | Benign | 0.002 | Benign | 4.11 | Benign | 0.03 | Affected | 3.77 | 5 | 0.1580 | 0.4779 | 0 | 3 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||
| c.3246G>T | Q1082H 2D AIThe SynGAP1 missense variant Q1082H is listed in gnomAD (ID 6‑33443798‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while only SIFT predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are not available. 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. | Likely Benign | 0.819762 | Disordered | 0.979325 | Binding | 0.347 | 0.896 | 0.875 | 6-33443798-G-T | -4.307 | Likely Benign | 0.273 | Likely Benign | Likely Benign | 0.092 | Likely Benign | -1.27 | Neutral | 0.002 | Benign | 0.002 | Benign | 4.11 | Benign | 0.03 | Affected | 3.77 | 5 | 0.1580 | 0.4779 | 0 | 3 | 0.3 | 9.01 | ||||||||||||||||||||||||||||||||||||
| c.3061C>A | Q1021K 2D AIThe SynGAP1 missense variant Q1021K is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a mixed signal: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments are limited: AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Given the predominance of benign calls in the consensus and the lack of a ClinVar pathogenic annotation, the variant is most likely benign, with no conflict with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -4.276 | Likely Benign | 0.786 | Likely Pathogenic | Ambiguous | 0.175 | Likely Benign | -1.79 | Neutral | 0.963 | Probably Damaging | 0.973 | Probably Damaging | 2.66 | Benign | 0.03 | Affected | 0.1551 | 0.4139 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3061C>G | Q1021E 2D AIThe SynGAP1 missense variant Q1021E is evaluated by multiple in silico tools. Benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The AlphaMissense‑Default tool gives an uncertain result. The consensus prediction from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus also indicates a likely benign effect. No Foldetta stability analysis is available for this residue. ClinVar contains no entry for this variant, and it is absent from gnomAD, so there is no external evidence to contradict the computational assessment. Based on the collective predictions, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -4.852 | Likely Benign | 0.545 | Ambiguous | Likely Benign | 0.137 | Likely Benign | -1.21 | Neutral | 0.963 | Probably Damaging | 0.973 | Probably Damaging | 2.65 | Benign | 0.03 | Affected | 0.1317 | 0.2069 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3062A>C | Q1021P 2D AIThe SynGAP1 missense variant Q1021P 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 also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1021P, 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 | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -3.522 | Likely Benign | 0.267 | Likely Benign | Likely Benign | 0.235 | Likely Benign | -2.11 | Neutral | 0.996 | Probably Damaging | 0.992 | Probably Damaging | 2.56 | Benign | 0.02 | Affected | 0.2022 | 0.4789 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3062A>G | Q1021R 2D AIThe SynGAP1 missense variant Q1021R is catalogued in gnomAD (ID 6‑33443614‑A‑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, resolves 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, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment 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 | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | 6-33443614-A-G | 1 | 6.20e-7 | -4.467 | Likely Benign | 0.770 | Likely Pathogenic | Likely Benign | 0.174 | Likely Benign | -1.80 | Neutral | 0.985 | Probably Damaging | 0.982 | Probably Damaging | 2.61 | Benign | 0.03 | Affected | 3.77 | 5 | 0.1257 | 0.2405 | 1 | 1 | -1.0 | 28.06 | ||||||||||||||||||||||||||||||||||
| c.3062A>T | Q1021L 2D AIThe SynGAP1 missense variant Q1021L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. 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. | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -5.780 | Likely Benign | 0.678 | Likely Pathogenic | Likely Benign | 0.226 | Likely Benign | -3.36 | Deleterious | 0.985 | Probably Damaging | 0.982 | Probably Damaging | 2.58 | Benign | 0.01 | Affected | 0.0688 | 0.5039 | -2 | -2 | 7.3 | -14.97 | ||||||||||||||||||||||||||||||||||||||||
| c.3063G>C | Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 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 status is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -4.694 | Likely Benign | 0.664 | Likely Pathogenic | Likely Benign | 0.184 | Likely Benign | -1.72 | Neutral | 0.996 | Probably Damaging | 0.995 | Probably Damaging | 2.61 | Benign | 0.01 | Affected | 0.1211 | 0.3601 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3063G>T | Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 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, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.979641 | Binding | 0.326 | 0.763 | 0.500 | -4.694 | Likely Benign | 0.664 | Likely Pathogenic | Likely Benign | 0.184 | Likely Benign | -1.72 | Neutral | 0.996 | Probably Damaging | 0.995 | Probably Damaging | 2.61 | Benign | 0.01 | Affected | 0.1211 | 0.3601 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3241G>A | A1081T 2D AIThe SynGAP1 missense variant A1081T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. 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, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.979759 | Binding | 0.288 | 0.895 | 0.750 | -3.887 | Likely Benign | 0.129 | Likely Benign | Likely Benign | 0.078 | Likely Benign | -1.07 | Neutral | 0.440 | Benign | 0.184 | Benign | 4.01 | Benign | 0.15 | Tolerated | 0.1567 | 0.6112 | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3241G>C | A1081P 2D AIThe SynGAP1 missense variant A1081P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.979759 | Binding | 0.288 | 0.895 | 0.750 | -2.967 | Likely Benign | 0.178 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -1.07 | Neutral | 0.005 | Benign | 0.010 | Benign | 4.00 | Benign | 0.14 | Tolerated | 0.1878 | 0.4540 | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3241G>T | A1081S 2D AIThe SynGAP1 missense variant A1081S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Consequently, 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 | 0.874069 | Disordered | 0.979759 | Binding | 0.288 | 0.895 | 0.750 | -3.536 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.078 | Likely Benign | -0.29 | Neutral | 0.021 | Benign | 0.031 | Benign | 4.02 | Benign | 0.23 | Tolerated | 0.2268 | 0.4915 | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| 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.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.3242C>T | A1081V 2D AIThe SynGAP1 missense variant A1081V is reported in gnomAD (ID 6‑33443794‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that A1081V is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.874069 | Disordered | 0.979759 | Binding | 0.288 | 0.895 | 0.750 | 6-33443794-C-T | -3.973 | Likely Benign | 0.172 | Likely Benign | Likely Benign | 0.036 | Likely Benign | -1.32 | Neutral | 0.611 | Possibly Damaging | 0.399 | Benign | 4.04 | Benign | 0.37 | Tolerated | 3.77 | 5 | 0.1353 | 0.4884 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||||
| c.3268A>C | N1090H 2D AIThe SynGAP1 missense variant N1090H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -3.744 | Likely Benign | 0.447 | Ambiguous | Likely Benign | 0.094 | Likely Benign | -1.42 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.67 | Benign | 0.10 | Tolerated | 0.1604 | 0.7550 | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||||||
| c.3268A>G | N1090D 2D AIThe SynGAP1 missense variant N1090D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and no Foldetta stability data is available. 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 | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -3.354 | Likely Benign | 0.827 | Likely Pathogenic | Ambiguous | 0.066 | Likely Benign | -1.39 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 2.70 | Benign | 0.47 | Tolerated | 0.1994 | 0.4375 | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3268A>T | N1090Y 2D AIThe SynGAP1 missense variant N1090Y is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect for the variant, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -4.744 | Likely Benign | 0.651 | Likely Pathogenic | Likely Benign | 0.139 | Likely Benign | -2.26 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.66 | Benign | 0.05 | Affected | 0.0661 | 0.5998 | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||||||
| c.3269A>C | N1090T 2D AIThe SynGAP1 missense variant N1090T is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (both HumDiv and HumVar tracks) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -3.478 | Likely Benign | 0.542 | Ambiguous | Likely Benign | 0.129 | Likely Benign | -0.78 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 2.77 | Benign | 0.58 | Tolerated | 0.1451 | 0.7930 | 0 | 0 | 2.8 | -13.00 | |||||||||||||||||||||||||||||||||||||||
| c.3269A>G | N1090S 2D AIThe SynGAP1 missense variant N1090S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -2.451 | Likely Benign | 0.228 | Likely Benign | Likely Benign | 0.135 | Likely Benign | -0.49 | Neutral | 0.997 | Probably Damaging | 0.983 | Probably Damaging | 2.97 | Benign | 0.38 | Tolerated | 0.3980 | 0.7620 | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||||||
| c.3269A>T | N1090I 2D AIThe SynGAP1 missense variant N1090I 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, reports the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the balance of evidence from both general and high‑accuracy predictors points to a benign classification, and this conclusion does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -4.356 | Likely Benign | 0.765 | Likely Pathogenic | Likely Benign | 0.173 | Likely Benign | -2.14 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.67 | Benign | 0.02 | Affected | 0.0781 | 0.6279 | -2 | -3 | 8.0 | -0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3270T>A | N1090K 2D AIThe SynGAP1 missense variant N1090K is reported in ClinVar as “None” and is present in gnomAD (ID 6‑33443822‑T‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) and the consensus result lean toward a benign interpretation. This conclusion does not contradict ClinVar, which currently has no pathogenic classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | 6-33443822-T-A | 2 | 1.28e-6 | -3.423 | Likely Benign | 0.963 | Likely Pathogenic | Likely Pathogenic | 0.053 | Likely Benign | -1.52 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.73 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.2147 | 0.6121 | 0 | 1 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||||||
| c.3270T>G | N1090K 2D AIThe SynGAP1 missense variant N1090K has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. The overall balance of evidence leans toward a benign interpretation, and this is consistent with the lack of a ClinVar classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.896620 | Disordered | 0.979886 | Binding | 0.341 | 0.887 | 1.000 | -3.423 | Likely Benign | 0.963 | Likely Pathogenic | Likely Pathogenic | 0.053 | Likely Benign | -1.52 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.73 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.2147 | 0.6121 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||
| c.4021G>A | A1341T 2D AIThe SynGAP1 missense variant A1341T is listed in ClinVar (ID 837815.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451895‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or likely benign. Only SIFT predicts a pathogenic effect. 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 unavailable. Overall, the preponderance of evidence points to a benign impact for A1341T, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | Conflicting | 3 | 6-33451895-G-A | 45 | 3.44e-5 | -3.224 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.099 | Likely Benign | -0.58 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.09 | Benign | 0.03 | Affected | 3.77 | 5 | 0.1835 | 0.7391 | 1 | 0 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||||
| c.4021G>C | A1341P 2D AIThe SynGAP1 missense variant A1341P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | -3.168 | Likely Benign | 0.112 | Likely Benign | Likely Benign | 0.117 | Likely Benign | -1.59 | Neutral | 0.131 | Benign | 0.057 | Benign | 4.02 | Benign | 0.02 | Affected | 0.2154 | 0.5703 | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||||||
| c.4021G>T | A1341S 2D AIThe SynGAP1 missense variant A1341S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6-33451895-G-T). All available in silico predictors agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | Uncertain | 1 | 6-33451895-G-T | -2.867 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.099 | Likely Benign | 0.80 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.40 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0.2784 | 0.5884 | 1 | 1 | -2.6 | 16.00 | ||||||||||||||||||||||||||||||||||
| c.4022C>A | A1341E 2D  AIThe SynGAP1 missense variant A1341E 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 call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign. Foldetta stability analysis is not available for this variant. Overall, the majority of 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 | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | -3.217 | Likely Benign | 0.307 | Likely Benign | Likely Benign | 0.056 | Likely Benign | -1.18 | Neutral | 0.012 | Benign | 0.015 | Benign | 4.05 | Benign | 0.01 | Affected | 0.1633 | 0.2624 | 0 | -1 | -5.3 | 58.04 | |||||||||||||||||||||||||||||||||||||||
| c.4022C>G | A1341G 2D AIThe SynGAP1 missense variant A1341G 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), 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. Only the SIFT algorithm predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Taken together, the preponderance of evidence points to a benign effect for A1341G, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar record, which contains no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | -3.334 | Likely Benign | 0.092 | Likely Benign | Likely Benign | 0.049 | Likely Benign | -0.84 | Neutral | 0.006 | Benign | 0.011 | Benign | 4.12 | Benign | 0.05 | Affected | 0.2026 | 0.4541 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.4022C>T | A1341V 2D AIThe SynGAP1 missense variant A1341V is catalogued in gnomAD (ID 6‑33451896‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign impact for A1341V, 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 | 0.823549 | Disordered | 0.980111 | Binding | 0.383 | 0.696 | 1.000 | 6-33451896-C-T | 1 | 6.29e-7 | -3.687 | Likely Benign | 0.131 | Likely Benign | Likely Benign | 0.066 | Likely Benign | -1.90 | Neutral | 0.006 | Benign | 0.011 | Benign | 4.04 | Benign | 0.02 | Affected | 3.77 | 5 | 0.1398 | 0.6557 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||
| c.2803G>A | A935T 2D AIThe SynGAP1 missense variant A935T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -4.247 | Likely Benign | 0.228 | Likely Benign | Likely Benign | 0.204 | Likely Benign | -1.27 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.33 | Pathogenic | 0.00 | Affected | 0.1670 | 0.6599 | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.2803G>C | A935P 2D AIThe SynGAP1 missense variant A935P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -3.239 | Likely Benign | 0.371 | Ambiguous | Likely Benign | 0.269 | Likely Benign | -2.08 | Neutral | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.29 | Pathogenic | 0.00 | Affected | 0.2062 | 0.5466 | 1 | -1 | -3.4 | 26.04 | ||||||||||||||||||||||||||||||||||||||||
| c.2803G>T | A935S 2D AIThe SynGAP1 missense variant A935S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the overall assessment. Overall, the majority of evidence points to a benign effect for A935S, 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 | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -3.361 | Likely Benign | 0.139 | Likely Benign | Likely Benign | 0.167 | Likely Benign | -0.60 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.53 | Benign | 0.00 | Affected | 0.2719 | 0.5496 | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2804C>A | A935D 2D AIThe SynGAP1 missense variant A935D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A935D, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -4.089 | Likely Benign | 0.817 | Likely Pathogenic | Ambiguous | 0.247 | Likely Benign | -2.69 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.31 | Pathogenic | 0.00 | Affected | 0.1832 | 0.1860 | 0 | -2 | -5.3 | 44.01 | |||||||||||||||||||||||||||||||||||||||
| c.2804C>G | A935G 2D AIThe SynGAP1 missense variant A935G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -2.868 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.152 | Likely Benign | -1.97 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.32 | Pathogenic | 0.00 | Affected | 0.2318 | 0.4679 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2804C>T | A935V 2D AIThe SynGAP1 missense variant A935V is not reported 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs. 1 pathogenic votes). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A935V, 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. | 0.736850 | Disordered | 0.980490 | Binding | 0.286 | 0.865 | 0.625 | -4.750 | Likely Benign | 0.397 | Ambiguous | Likely Benign | 0.194 | Likely Benign | -2.06 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.30 | Pathogenic | 0.00 | Affected | 0.1340 | 0.5941 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||||||||||||
| c.2875C>A | H959N 2D AIThe SynGAP1 missense variant H959N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only ESM1b predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors and high‑accuracy tools indicates that H959N 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 | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.811 | Likely Pathogenic | 0.104 | Likely Benign | Likely Benign | 0.115 | Likely Benign | -0.10 | Neutral | 0.144 | Benign | 0.058 | Benign | 4.15 | Benign | 0.21 | Tolerated | 0.2298 | 0.3838 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2875C>G | H959D 2D AIThe SynGAP1 missense variant H959D is listed in gnomAD (ID 6‑33443427‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to “Likely Benign” (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none reported). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | 6-33443427-C-G | 1 | 6.20e-7 | -12.060 | Likely Pathogenic | 0.235 | Likely Benign | Likely Benign | 0.176 | Likely Benign | -0.73 | Neutral | 0.144 | Benign | 0.058 | Benign | 4.14 | Benign | 0.29 | Tolerated | 3.77 | 5 | 0.2586 | 0.3066 | -1 | 1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||||||
| c.2875C>T | H959Y 2D AIThe SynGAP1 missense variant H959Y is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a tolerated change, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as Likely Benign. In contrast, polyPhen‑2 HumDiv, SIFT, and ESM1b predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for H959Y, 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 | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.367 | Likely Pathogenic | 0.146 | Likely Benign | Likely Benign | 0.140 | Likely Benign | -1.09 | Neutral | 0.510 | Possibly Damaging | 0.147 | Benign | 4.09 | Benign | 0.05 | Affected | 0.1672 | 0.4906 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2876A>C | H959P 2D AIThe SynGAP1 missense variant H959P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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 | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.902 | Likely Pathogenic | 0.070 | Likely Benign | Likely Benign | 0.232 | Likely Benign | -0.61 | Neutral | 0.453 | Possibly Damaging | 0.105 | Benign | 4.14 | Benign | 0.38 | Tolerated | 0.2284 | 0.4901 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2876A>G | H959R 2D AIThe SynGAP1 missense variant H959R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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 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, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -9.459 | Likely Pathogenic | 0.182 | Likely Benign | Likely Benign | 0.162 | Likely Benign | -1.11 | Neutral | 0.144 | Benign | 0.078 | Benign | 4.14 | Benign | 0.15 | Tolerated | 0.2416 | 0.3610 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2876A>T | H959L 2D AIThe SynGAP1 missense variant H959L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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 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 H959L 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 | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.515 | Likely Pathogenic | 0.100 | Likely Benign | Likely Benign | 0.236 | Likely Benign | -1.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.14 | Benign | 0.09 | Tolerated | 0.1698 | 0.5538 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2877C>A | H959Q 2D AIThe SynGAP1 missense variant H959Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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) reports it as likely benign. Only ESM1b predicts a pathogenic outcome, representing the sole discordant signal. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H959Q 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 | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.657 | Likely Pathogenic | 0.126 | Likely Benign | Likely Benign | 0.182 | Likely Benign | -0.77 | Neutral | 0.255 | Benign | 0.105 | Benign | 4.15 | Benign | 0.10 | Tolerated | 0.2264 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2877C>G | H959Q 2D AIThe SynGAP1 missense variant H959Q 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), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the single pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H959Q 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. | Likely Benign | 0.985964 | Disordered | 0.980566 | Binding | 0.333 | 0.905 | 0.750 | -8.657 | Likely Pathogenic | 0.126 | Likely Benign | Likely Benign | 0.182 | Likely Benign | -0.77 | Neutral | 0.255 | Benign | 0.105 | Benign | 4.15 | Benign | 0.10 | Tolerated | 0.2264 | 0.3936 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3202T>A | L1068M 2D AIThe SynGAP1 missense variant L1068M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -5.739 | Likely Benign | 0.120 | Likely Benign | Likely Benign | 0.043 | Likely Benign | -0.22 | Neutral | 0.977 | Probably Damaging | 0.721 | Possibly Damaging | 2.49 | Pathogenic | 0.00 | Affected | 0.0930 | 0.4582 | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3202T>G | L1068V 2D AIThe SynGAP1 missense variant L1068V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -5.325 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -0.58 | Neutral | 0.451 | Benign | 0.110 | Benign | 2.54 | Benign | 0.00 | Affected | 0.1619 | 0.4404 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3203T>C | L1068S 2D  AIThe SynGAP1 missense variant L1068S 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, polyPhen‑2 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 AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -6.297 | Likely Benign | 0.211 | Likely Benign | Likely Benign | 0.175 | Likely Benign | -0.57 | Neutral | 0.032 | Benign | 0.017 | Benign | 2.59 | Benign | 0.00 | Affected | 0.2810 | 0.1853 | -3 | -2 | -4.6 | -26.08 | |||||||||||||||||||||||||||||||||||||||
| c.3203T>G | L1068W 2D  AIThe SynGAP1 missense variant L1068W 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, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves as pathogenic, and Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for L1068W. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -8.574 | Likely Pathogenic | 0.342 | Ambiguous | Likely Benign | 0.151 | Likely Benign | -1.96 | Neutral | 0.994 | Probably Damaging | 0.884 | Possibly Damaging | 2.46 | Pathogenic | 0.00 | Affected | 0.0742 | 0.3763 | -2 | -2 | -4.7 | 73.05 | ||||||||||||||||||||||||||||||||||||||||
| c.3204G>C | L1068F 2D AIThe SynGAP1 missense variant L1068F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) favor a benign classification. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -6.338 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.107 | Likely Benign | -1.38 | Neutral | 0.934 | Possibly Damaging | 0.537 | Possibly Damaging | 2.49 | Pathogenic | 0.00 | Affected | 0.0754 | 0.4202 | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.3204G>T | L1068F 2D AIThe SynGAP1 missense variant L1068F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) favor a benign classification. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.947281 | Disordered | 0.981041 | Binding | 0.362 | 0.907 | 0.875 | -6.338 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.106 | Likely Benign | -1.38 | Neutral | 0.934 | Possibly Damaging | 0.537 | Possibly Damaging | 2.49 | Pathogenic | 0.00 | Affected | 0.0754 | 0.4202 | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.3280T>A | S1094T 2D AIThe SynGAP1 missense variant S1094T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | -4.009 | Likely Benign | 0.194 | Likely Benign | Likely Benign | 0.077 | Likely Benign | -0.57 | Neutral | 0.790 | Possibly Damaging | 0.433 | Benign | 2.59 | Benign | 0.16 | Tolerated | 0.1874 | 0.6902 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3280T>C | S1094P 2D AIThe SynGAP1 missense variant S1094P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S1094P, 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 | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | -2.430 | Likely Benign | 0.285 | Likely Benign | Likely Benign | 0.124 | Likely Benign | -1.31 | Neutral | 0.990 | Probably Damaging | 0.798 | Possibly Damaging | 2.46 | Pathogenic | 0.13 | Tolerated | 0.2322 | 0.6099 | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3280T>G | S1094A 2D AIThe SynGAP1 missense variant S1094A 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, so the pathogenic‑prediction group is empty. 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 results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | -3.595 | Likely Benign | 0.188 | Likely Benign | Likely Benign | 0.117 | Likely Benign | -0.78 | Neutral | 0.447 | Benign | 0.252 | Benign | 2.66 | Benign | 1.00 | Tolerated | 0.4692 | 0.5403 | 1 | 1 | 2.6 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3281C>A | S1094Y 2D AIThe SynGAP1 missense variant S1094Y is not reported in ClinVar (status: none) but is present in gnomAD (ID 6‑33443833‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding‑stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore show a benign call from AlphaMissense‑Optimized, an inconclusive SGM Consensus, and no Foldetta data. Overall, the balance of evidence leans toward a pathogenic interpretation (five pathogenic versus four benign calls), and this does not contradict the ClinVar status, which currently has no assertion for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | 6-33443833-C-A | -5.609 | Likely Benign | 0.631 | Likely Pathogenic | Likely Benign | 0.155 | Likely Benign | -2.07 | Neutral | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 2.45 | Pathogenic | 0.02 | Affected | 3.77 | 5 | 0.1007 | 0.5877 | -2 | -3 | -0.5 | 76.10 | |||||||||||||||||||||||||||||||||||||
| c.3281C>G | S1094C 2D AIThe SynGAP1 missense variant S1094C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools—AlphaMissense‑Default and ESM1b—return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized indicates a benign effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields no clear consensus and is treated as unavailable; Foldetta data are not provided, so its stability prediction is also unavailable. 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. | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | -7.143 | In-Between | 0.425 | Ambiguous | Likely Benign | 0.131 | Likely Benign | -1.81 | Neutral | 0.997 | Probably Damaging | 0.946 | Probably Damaging | 2.45 | Pathogenic | 0.05 | Affected | 0.1403 | 0.6309 | 0 | -1 | 3.3 | 16.06 | ||||||||||||||||||||||||||||||||||||||||
| c.3281C>T | S1094F 2D AIThe SynGAP1 missense variant S1094F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy tool predicts benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the 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. | 0.938133 | Disordered | 0.981352 | Binding | 0.358 | 0.877 | 1.000 | -5.655 | Likely Benign | 0.666 | Likely Pathogenic | Likely Benign | 0.150 | Likely Benign | -2.17 | Neutral | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 2.45 | Pathogenic | 0.02 | Affected | 0.0925 | 0.5851 | -3 | -2 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||||||
| c.3238G>A | A1080T 2D AIThe SynGAP1 missense variant A1080T (ClinVar ID 1473274.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (ID 6‑33443790‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “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, 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 | 0.912647 | Disordered | 0.981457 | Binding | 0.303 | 0.900 | 0.750 | Conflicting | 2 | 6-33443790-G-A | 17 | 1.06e-5 | -3.928 | Likely Benign | 0.133 | Likely Benign | Likely Benign | 0.144 | Likely Benign | -0.19 | Neutral | 0.253 | Benign | 0.042 | Benign | 4.10 | Benign | 0.60 | Tolerated | 3.77 | 5 | 0.1564 | 0.7103 | 1 | 0 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||||
| 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.3238G>T | A1080S 2D AIThe SynGAP1 missense variant A1080S is listed in ClinVar (ID 2703014.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443790‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect, 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 | 0.912647 | Disordered | 0.981457 | Binding | 0.303 | 0.900 | 0.750 | Uncertain | 1 | 6-33443790-G-T | 1 | 6.26e-7 | -3.277 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.103 | Likely Benign | 0.01 | Neutral | 0.702 | Possibly Damaging | 0.346 | Benign | 4.16 | Benign | 0.08 | Tolerated | 3.77 | 5 | 0.2498 | 0.5915 | 1 | 1 | -2.6 | 16.00 | ||||||||||||||||||||||||||||||||
| c.3239C>A | A1080E 2D AIThe SynGAP1 missense variant A1080E is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443791‑C‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic outcome are polyPhen‑2 (HumDiv and 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 assessment is available. High‑accuracy evidence therefore points to a benign or uncertain impact: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is benign, and Foldetta data are missing. Overall, the balance of predictions leans toward a benign effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.912647 | Disordered | 0.981457 | Binding | 0.303 | 0.900 | 0.750 | 6-33443791-C-A | -3.672 | Likely Benign | 0.855 | Likely Pathogenic | Ambiguous | 0.090 | Likely Benign | -1.50 | Neutral | 0.901 | Possibly Damaging | 0.540 | Possibly Damaging | 4.00 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1394 | 0.2437 | -1 | 0 | -5.3 | 58.04 | ||||||||||||||||||||||||||||||||||||
| c.3239C>G | A1080G 2D AIThe SynGAP1 missense variant A1080G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the consensus of the majority of prediction algorithms and the high‑accuracy tools points to a benign effect for A1080G, with no conflict with ClinVar status. 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 | -3.515 | Likely Benign | 0.213 | Likely Benign | Likely Benign | 0.089 | Likely Benign | -0.80 | Neutral | 0.901 | Possibly Damaging | 0.355 | Benign | 4.00 | Benign | 0.04 | Affected | 0.2153 | 0.4958 | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| 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.3205C>A | Q1069K 2D AIThe SynGAP1 missense variant Q1069K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of computational evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -5.080 | Likely Benign | 0.542 | Ambiguous | Likely Benign | 0.099 | Likely Benign | -0.88 | Neutral | 0.625 | Possibly Damaging | 0.266 | Benign | 2.77 | Benign | 0.28 | Tolerated | 0.1904 | 0.5071 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3205C>G | Q1069E 2D AIThe SynGAP1 missense variant Q1069E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -5.165 | Likely Benign | 0.322 | Likely Benign | Likely Benign | 0.107 | Likely Benign | -0.68 | Neutral | 0.451 | Benign | 0.266 | Benign | 2.76 | Benign | 0.33 | Tolerated | 0.1460 | 0.3127 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3206A>C | Q1069P 2D AIThe SynGAP1 missense variant Q1069P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -3.458 | Likely Benign | 0.056 | Likely Benign | Likely Benign | 0.211 | Likely Benign | 0.75 | Neutral | 0.977 | Probably Damaging | 0.722 | Possibly Damaging | 2.73 | Benign | 1.00 | Tolerated | 0.2179 | 0.5944 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3206A>G | Q1069R 2D AIThe SynGAP1 missense variant Q1069R 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -3.257 | Likely Benign | 0.467 | Ambiguous | Likely Benign | 0.094 | Likely Benign | -1.17 | Neutral | 0.666 | Possibly Damaging | 0.355 | Benign | 2.73 | Benign | 0.21 | Tolerated | 0.1557 | 0.3114 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3206A>T | Q1069L 2D AIThe SynGAP1 missense variant Q1069L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -4.278 | Likely Benign | 0.141 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -0.96 | Neutral | 0.003 | Benign | 0.008 | Benign | 2.83 | Benign | 0.10 | Tolerated | 0.0936 | 0.6624 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3207G>C | Q1069H 2D AIThe SynGAP1 missense variant Q1069H is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -4.723 | Likely Benign | 0.306 | Likely Benign | Likely Benign | 0.085 | Likely Benign | -1.31 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.69 | Benign | 0.06 | Tolerated | 0.1560 | 0.4678 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3207G>T | Q1069H 2D AIThe SynGAP1 missense variant Q1069H is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.943310 | Disordered | 0.981477 | Binding | 0.333 | 0.906 | 0.875 | -4.723 | Likely Benign | 0.306 | Likely Benign | Likely Benign | 0.085 | Likely Benign | -1.31 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.69 | Benign | 0.06 | Tolerated | 0.1560 | 0.4678 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.4024G>A | D1342N 2D AIThe SynGAP1 missense variant D1342N is catalogued in gnomAD (ID 6‑33451898‑G‑A) but has no ClinVar submission. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated or benign. Grouping by consensus, all listed predictors fall into the benign category, with no tool reporting pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta stability analysis is unavailable for this variant. Consequently, the aggregate 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 | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | 6-33451898-G-A | -3.459 | Likely Benign | 0.140 | Likely Benign | Likely Benign | 0.058 | Likely Benign | 0.29 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.07 | Benign | 0.93 | Tolerated | 4.32 | 4 | 0.1868 | 0.6022 | 1 | 2 | 0.0 | -0.98 | ||||||||||||||||||||||||||||||||||||
| c.4024G>C | D1342H 2D AIThe SynGAP1 missense variant D1342H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of available predictions indicates that D1342H 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 | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | -3.765 | Likely Benign | 0.310 | Likely Benign | Likely Benign | 0.039 | Likely Benign | -0.56 | Neutral | 0.834 | Possibly Damaging | 0.400 | Benign | 4.00 | Benign | 0.02 | Affected | 0.2365 | 0.6177 | 1 | -1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||||||
| 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.4025A>C | D1342A 2D AIThe SynGAP1 missense variant D1342A 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. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for D1342A, 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 | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | -2.719 | Likely Benign | 0.145 | Likely Benign | Likely Benign | 0.049 | Likely Benign | -0.58 | Neutral | 0.371 | Benign | 0.084 | Benign | 4.06 | Benign | 0.02 | Affected | 0.4270 | 0.5676 | 0 | -2 | 5.3 | -44.01 | |||||||||||||||||||||||||||||||||||||||
| c.4025A>G | D1342G 2D AIThe SynGAP1 missense variant D1342G is reported in gnomAD (variant ID 6‑33451899‑A‑G) but has no ClinVar entry. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective 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 | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | 6-33451899-A-G | 1 | 7.29e-7 | -3.227 | Likely Benign | 0.129 | Likely Benign | Likely Benign | 0.021 | Likely Benign | -0.89 | Neutral | 0.225 | Benign | 0.045 | Benign | 4.05 | Benign | 0.09 | Tolerated | 4.32 | 4 | 0.3633 | 0.5601 | -1 | 1 | 3.1 | -58.04 | ||||||||||||||||||||||||||||||||||
| c.4025A>T | D1342V 2D AIThe SynGAP1 missense variant D1342V 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, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is 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 | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | -2.890 | Likely Benign | 0.317 | Likely Benign | Likely Benign | 0.089 | Likely Benign | -1.27 | Neutral | 0.588 | Possibly Damaging | 0.212 | Benign | 4.01 | Benign | 0.00 | Affected | 0.1214 | 0.5617 | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||||||
| c.4026C>A | D1342E 2D AIThe SynGAP1 missense variant D1342E is catalogued in gnomAD (ID 6‑33451900‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes. Only SIFT predicts 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 this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that D1342E is most likely benign, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | 6-33451900-C-A | -3.169 | Likely Benign | 0.134 | Likely Benign | Likely Benign | 0.026 | Likely Benign | -0.88 | Neutral | 0.225 | Benign | 0.084 | Benign | 4.16 | Benign | 0.04 | Affected | 4.32 | 4 | 0.2130 | 0.5720 | 2 | 3 | 0.0 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.4026C>G | D1342E 2D AIThe SynGAP1 missense variant D1342E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions points to a benign effect for D1342E, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.921076 | Disordered | 0.981682 | Binding | 0.316 | 0.678 | 0.875 | -3.169 | Likely Benign | 0.134 | Likely Benign | Likely Benign | 0.026 | Likely Benign | -0.88 | Neutral | 0.225 | Benign | 0.084 | Benign | 4.16 | Benign | 0.04 | Affected | 4.32 | 4 | 0.2130 | 0.5720 | 2 | 3 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||
| c.2776T>A | S926T 2D AIThe SynGAP1 missense variant S926T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) is inconclusive, with two pathogenic and two benign votes. AlphaMissense‑Optimized, a high‑accuracy model, predicts benign, while Foldetta stability analysis is unavailable. Overall, the majority of standard tools favor a pathogenic effect, whereas the single high‑accuracy model suggests benign. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -2.917 | Likely Benign | 0.651 | Likely Pathogenic | Likely Benign | 0.226 | Likely Benign | -2.34 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.55 | Pathogenic | 0.00 | Affected | 0.1174 | 0.5663 | 1 | 1 | 0.1 | 14.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2776T>C | S926P 2D AIThe SynGAP1 missense variant S926P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (pathogenic), and PROVEAN (pathogenic), yielding a Likely Pathogenic classification. AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S926P. 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 | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -3.873 | Likely Benign | 0.916 | Likely Pathogenic | Ambiguous | 0.424 | Likely Benign | -3.79 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.51 | Pathogenic | 0.00 | Affected | 0.1738 | 0.5058 | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||||||
| c.2776T>G | S926A 2D AIThe SynGAP1 missense variant S926A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors 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 reliable predictions indicate 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. | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -3.042 | Likely Benign | 0.463 | Ambiguous | Likely Benign | 0.186 | Likely Benign | -2.13 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.59 | Pathogenic | 0.00 | Affected | 0.4657 | 0.4488 | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||||||||
| c.2777C>A | S926Y 2D AIThe SynGAP1 missense variant S926Y 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S926Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -6.602 | Likely Benign | 0.968 | Likely Pathogenic | Likely Pathogenic | 0.444 | Likely Benign | -4.53 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 1.50 | Pathogenic | 0.00 | Affected | 0.0602 | 0.4932 | -3 | -2 | -0.5 | 76.10 | |||||||||||||||||||||||||||||||||||||||
| c.2777C>G | S926C 2D AIThe SynGAP1 missense variant S926C is not 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, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of predictions lean toward pathogenicity, with the high‑accuracy AlphaMissense‑Optimized result providing a conflicting benign signal. Thus, the variant is most likely pathogenic based on the collective evidence, 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 | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -6.546 | Likely Benign | 0.680 | Likely Pathogenic | Likely Benign | 0.414 | Likely Benign | -3.81 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 1.50 | Pathogenic | 0.00 | Affected | 0.0815 | 0.5487 | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||||||
| c.2777C>T | S926F 2D AIThe SynGAP1 missense variant S926F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S926F 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 | 0.461924 | Structured | 0.981753 | Binding | 0.295 | 0.854 | 0.250 | -6.157 | Likely Benign | 0.980 | Likely Pathogenic | Likely Pathogenic | 0.458 | Likely Benign | -4.57 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 1.50 | Pathogenic | 0.00 | Affected | 0.0585 | 0.5220 | -3 | -2 | 3.6 | 60.10 | |||||||||||||||||||||||||||||||||||||||
| c.2890C>A | H964N 2D AIThe SynGAP1 missense variant H964N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -8.073 | Likely Pathogenic | 0.084 | Likely Benign | Likely Benign | 0.098 | Likely Benign | -0.30 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.64 | Tolerated | 0.1988 | 0.3495 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2890C>G | H964D 2D AIThe SynGAP1 missense variant H964D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -11.061 | Likely Pathogenic | 0.207 | Likely Benign | Likely Benign | 0.124 | Likely Benign | -0.45 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.24 | Tolerated | 0.2313 | 0.2923 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2890C>T | H964Y 2D AIThe SynGAP1 missense variant H964Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and the Foldetta stability analysis is unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -7.385 | In-Between | 0.139 | Likely Benign | Likely Benign | 0.069 | Likely Benign | -1.13 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.11 | Benign | 0.02 | Affected | 0.1422 | 0.4363 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2891A>C | H964P 2D AIThe SynGAP1 missense variant H964P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while the only pathogenic call comes from SIFT. ESM1b is uncertain, and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta stability analysis is unavailable. Overall, the collective evidence points to a benign impact for H964P, 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 | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -7.466 | In-Between | 0.063 | Likely Benign | Likely Benign | 0.156 | Likely Benign | -0.34 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.12 | Benign | 0.04 | Affected | 0.1978 | 0.4301 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2891A>G | H964R 2D AIThe SynGAP1 missense variant H964R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b. The SGM‑Consensus, which is a 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 assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -8.275 | Likely Pathogenic | 0.163 | Likely Benign | Likely Benign | 0.129 | Likely Benign | -0.68 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.19 | Benign | 0.05 | Affected | 0.2237 | 0.3467 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2891A>T | H964L 2D AIThe SynGAP1 missense variant H964L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -7.568 | In-Between | 0.092 | Likely Benign | Likely Benign | 0.129 | Likely Benign | -1.20 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.15 | Benign | 0.02 | Affected | 0.1409 | 0.5195 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2892C>A | H964Q 2D AIThe SynGAP1 missense variant H964Q is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. The only tool with an uncertain call is ESM1b, and no pathogenic predictions are reported. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -7.279 | In-Between | 0.102 | Likely Benign | Likely Benign | 0.058 | Likely Benign | -0.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.07 | Tolerated | 0.1969 | 0.3593 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2892C>G | H964Q 2D AIThe SynGAP1 missense variant H964Q 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only uncertain result comes from ESM1b. The high‑accuracy consensus methods also support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the evidence overwhelmingly indicates that H964Q is most likely benign, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.990547 | Disordered | 0.982486 | Binding | 0.364 | 0.886 | 0.750 | -7.279 | In-Between | 0.102 | Likely Benign | Likely Benign | 0.058 | Likely Benign | -0.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.07 | Tolerated | 0.1969 | 0.3593 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| 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.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.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.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.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.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.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.3112A>C | T1038P 2D AIThe SynGAP1 missense variant T1038P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -2.196 | Likely Benign | 0.390 | Ambiguous | Likely Benign | 0.116 | Likely Benign | -1.10 | Neutral | 0.965 | Probably Damaging | 0.611 | Possibly Damaging | 2.66 | Benign | 0.26 | Tolerated | 0.1856 | 0.4680 | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3112A>G | T1038A 2D AIThe SynGAP1 missense variant T1038A 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, whereas only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of 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 | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -3.544 | Likely Benign | 0.265 | Likely Benign | Likely Benign | 0.047 | Likely Benign | -0.79 | Neutral | 0.649 | Possibly Damaging | 0.209 | Benign | 2.81 | Benign | 0.15 | Tolerated | 0.3429 | 0.3983 | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3112A>T | T1038S 2D AIThe SynGAP1 missense variant T1038S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -2.693 | Likely Benign | 0.198 | Likely Benign | Likely Benign | 0.101 | Likely Benign | -0.17 | Neutral | 0.649 | Possibly Damaging | 0.209 | Benign | 2.98 | Benign | 0.74 | Tolerated | 0.2879 | 0.4035 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3113C>A | T1038N 2D AIThe SynGAP1 missense variant T1038N is not reported in ClinVar and has no entries in gnomAD, indicating it has not been catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, while the majority‑vote consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. No Foldetta stability analysis is available, so folding‑stability evidence is lacking. Overall, the preponderance of computational evidence supports a benign classification for T1038N, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this is not contradicted by ClinVar, which has no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -3.837 | Likely Benign | 0.390 | Ambiguous | Likely Benign | 0.054 | Likely Benign | -1.36 | Neutral | 0.818 | Possibly Damaging | 0.355 | Benign | 2.68 | Benign | 0.10 | Tolerated | 0.1184 | 0.4490 | 0 | 0 | -2.8 | 13.00 | |||||||||||||||||||||||||||||||||||||||
| c.3113C>G | T1038S 2D AIThe SynGAP1 missense variant T1038S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -2.693 | Likely Benign | 0.198 | Likely Benign | Likely Benign | 0.102 | Likely Benign | -0.17 | Neutral | 0.649 | Possibly Damaging | 0.209 | Benign | 2.98 | Benign | 0.74 | Tolerated | 0.2879 | 0.4035 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3113C>T | T1038I 2D AIThe SynGAP1 T1038I missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the balance of evidence leans toward a benign interpretation, with one high‑accuracy tool inconclusive and no conflicting ClinVar annotation. Thus, the variant is most likely benign, and there is no ClinVar status that contradicts this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.938133 | Disordered | 0.982911 | Binding | 0.279 | 0.794 | 0.625 | -4.552 | Likely Benign | 0.877 | Likely Pathogenic | Ambiguous | 0.093 | Likely Benign | -2.02 | Neutral | 0.990 | Probably Damaging | 0.637 | Possibly Damaging | 2.69 | Benign | 0.04 | Affected | 0.1012 | 0.5036 | 0 | -1 | 5.2 | 12.05 | |||||||||||||||||||||||||||||||||||||||
| c.3277C>A | Q1093K 2D AIThe SynGAP1 missense variant Q1093K is reported in gnomAD (variant ID 6‑33443829‑C‑A) but has no ClinVar entry. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts benign. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | 6-33443829-C-A | -3.919 | Likely Benign | 0.558 | Ambiguous | Likely Benign | 0.061 | Likely Benign | -0.92 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.78 | Benign | 0.06 | Tolerated | 3.77 | 5 | 0.1926 | 0.5861 | 1 | 1 | -0.4 | 0.04 | ||||||||||||||||||||||||||||||||||||
| c.3277C>G | Q1093E 2D AIThe SynGAP1 missense change Q1093E is not reported in ClinVar and is absent from gnomAD. In silico assessment shows unanimous benign predictions: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. No tool predicts pathogenicity. High‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” The protein‑folding stability predictor Foldetta was not available for this variant. Overall, the evidence strongly supports a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign and does not contradict existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | -3.104 | Likely Benign | 0.265 | Likely Benign | Likely Benign | 0.047 | Likely Benign | -0.59 | Neutral | 0.112 | Benign | 0.041 | Benign | 2.78 | Benign | 0.07 | Tolerated | 0.1514 | 0.3717 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3278A>C | Q1093P 2D AIThe SynGAP1 missense variant Q1093P is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors classifies it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic effect. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely benign, while Foldetta stability analysis is unavailable. Overall, the evidence points to a benign effect for Q1093P, 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 | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | -2.613 | Likely Benign | 0.080 | Likely Benign | Likely Benign | 0.137 | Likely Benign | -0.96 | Neutral | 0.001 | Benign | 0.001 | Benign | 2.69 | Benign | 0.05 | Affected | 0.2059 | 0.5956 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3278A>G | Q1093R 2D AIThe SynGAP1 missense variant Q1093R is reported in gnomAD (ID 6‑33443830‑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, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | 6-33443830-A-G | 1 | 6.40e-7 | -3.681 | Likely Benign | 0.483 | Ambiguous | Likely Benign | 0.065 | Likely Benign | -1.06 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.73 | Benign | 0.04 | Affected | 3.77 | 5 | 0.1537 | 0.3904 | 1 | 1 | -1.0 | 28.06 | ||||||||||||||||||||||||||||||||||
| c.3278A>T | Q1093L 2D AIThe SynGAP1 missense variant Q1093L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | -3.242 | Likely Benign | 0.165 | Likely Benign | Likely Benign | 0.055 | Likely Benign | -1.10 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.72 | Benign | 0.03 | Affected | 0.0899 | 0.6837 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3279G>C | Q1093H 2D AIThe SynGAP1 missense variant Q1093H is not reported 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. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | -4.003 | Likely Benign | 0.337 | Likely Benign | Likely Benign | 0.060 | Likely Benign | -1.14 | Neutral | 0.002 | Benign | 0.003 | Benign | 2.69 | Benign | 0.02 | Affected | 0.1600 | 0.5269 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3279G>T | Q1093H 2D AIThe SynGAP1 missense variant Q1093H is not reported 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. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983312 | Binding | 0.351 | 0.886 | 1.000 | -4.003 | Likely Benign | 0.337 | Likely Benign | Likely Benign | 0.060 | Likely Benign | -1.14 | Neutral | 0.002 | Benign | 0.003 | Benign | 2.69 | Benign | 0.02 | Affected | 0.1600 | 0.5269 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2878C>A | H960N 2D AIThe SynGAP1 missense variant H960N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -8.822 | Likely Pathogenic | 0.101 | Likely Benign | Likely Benign | 0.130 | Likely Benign | -0.57 | Neutral | 0.494 | Possibly Damaging | 0.129 | Benign | 4.19 | Benign | 0.40 | Tolerated | 0.2137 | 0.3695 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2878C>G | H960D 2D AIThe SynGAP1 missense variant H960D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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 | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -12.235 | Likely Pathogenic | 0.243 | Likely Benign | Likely Benign | 0.147 | Likely Benign | -1.09 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.19 | Benign | 0.31 | Tolerated | 0.2504 | 0.2923 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2878C>T | H960Y 2D AIThe SynGAP1 missense variant H960Y is reported in gnomAD (ID 6‑33443430‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools predict pathogenicity—polyPhen‑2 HumDiv and ESM1b—while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of prediction algorithms and the high‑accuracy tools 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 | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | 6-33443430-C-T | 1 | 6.20e-7 | -8.181 | Likely Pathogenic | 0.158 | Likely Benign | Likely Benign | 0.097 | Likely Benign | -1.25 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.13 | Benign | 0.21 | Tolerated | 3.77 | 5 | 0.1446 | 0.4963 | 2 | 0 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||
| c.2879A>C | H960P 2D AIThe SynGAP1 missense variant H960P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -8.672 | Likely Pathogenic | 0.064 | Likely Benign | Likely Benign | 0.119 | Likely Benign | -0.95 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.18 | Benign | 0.28 | Tolerated | 0.2157 | 0.4901 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2879A>G | H960R 2D AIThe SynGAP1 missense variant H960R is reported in gnomAD (ID 6‑33443431‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools predict pathogenicity—polyPhen‑2 HumDiv and ESM1b—while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports likely benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | 6-33443431-A-G | 1 | 6.20e-7 | -9.238 | Likely Pathogenic | 0.192 | Likely Benign | Likely Benign | 0.075 | Likely Benign | -1.10 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.19 | Benign | 0.25 | Tolerated | 3.77 | 5 | 0.2237 | 0.3667 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||||
| c.2879A>T | H960L 2D AIThe SynGAP1 missense variant H960L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates 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 | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -8.386 | Likely Pathogenic | 0.108 | Likely Benign | Likely Benign | 0.130 | Likely Benign | -1.30 | Neutral | 0.174 | Benign | 0.043 | Benign | 4.17 | Benign | 0.33 | Tolerated | 0.1465 | 0.5595 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2880C>A | H960Q 2D AIThe SynGAP1 missense variant H960Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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 | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -8.551 | Likely Pathogenic | 0.124 | Likely Benign | Likely Benign | 0.109 | Likely Benign | -0.79 | Neutral | 0.748 | Possibly Damaging | 0.170 | Benign | 4.20 | Benign | 0.21 | Tolerated | 0.2045 | 0.3993 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2880C>G | H960Q 2D AIThe SynGAP1 missense variant H960Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.987911 | Disordered | 0.983385 | Binding | 0.380 | 0.901 | 0.750 | -8.551 | Likely Pathogenic | 0.124 | Likely Benign | Likely Benign | 0.109 | Likely Benign | -0.79 | Neutral | 0.748 | Possibly Damaging | 0.170 | Benign | 4.20 | Benign | 0.21 | Tolerated | 0.2045 | 0.3993 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.4027C>A | H1343N 2D AIThe SynGAP1 missense variant H1343N is not reported 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, also indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | -3.077 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.043 | Likely Benign | -1.09 | Neutral | 0.444 | Benign | 0.071 | Benign | 4.06 | Benign | 0.00 | Affected | 0.2398 | 0.3299 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.4027C>G | H1343D 2D AIThe SynGAP1 missense variant H1343D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only SIFT predicts a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. AlphaMissense‑Optimized also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | -3.136 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.051 | Likely Benign | -1.29 | Neutral | 0.444 | Benign | 0.071 | Benign | 4.07 | Benign | 0.00 | Affected | 0.3011 | 0.2403 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.4027C>T | H1343Y 2D AIThe SynGAP1 missense variant H1343Y is reported in gnomAD (ID 6‑33451901‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for H1343Y, 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 | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | 6-33451901-C-T | -3.479 | Likely Benign | 0.139 | Likely Benign | Likely Benign | 0.040 | Likely Benign | -0.85 | Neutral | 0.444 | Benign | 0.071 | Benign | 4.06 | Benign | 0.00 | Affected | 4.32 | 1 | 0.1030 | 0.4792 | 2 | 0 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||||
| c.4028A>C | H1343P 2D AIThe SynGAP1 missense variant H1343P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | -2.696 | Likely Benign | 0.094 | Likely Benign | Likely Benign | 0.126 | Likely Benign | -1.23 | Neutral | 0.659 | Possibly Damaging | 0.104 | Benign | 4.02 | Benign | 0.00 | Affected | 0.2333 | 0.4220 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.4028A>G | H1343R 2D AIThe SynGAP1 missense variant H1343R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | -2.179 | Likely Benign | 0.105 | Likely Benign | Likely Benign | 0.069 | Likely Benign | -1.16 | Neutral | 0.659 | Possibly Damaging | 0.071 | Benign | 4.08 | Benign | 0.00 | Affected | 0.2301 | 0.2602 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.4028A>T | H1343L 2D AIThe SynGAP1 missense variant H1343L is reported in gnomAD (ID 6‑33451902‑A‑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 substitution 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 available predictions points to a benign effect, 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 | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | 6-33451902-A-T | -1.552 | Likely Benign | 0.132 | Likely Benign | Likely Benign | 0.058 | Likely Benign | -1.28 | Neutral | 0.053 | Benign | 0.012 | Benign | 4.07 | Benign | 0.00 | Affected | 4.32 | 1 | 0.1222 | 0.5869 | -3 | -2 | 7.0 | -23.98 | ||||||||||||||||||||||||||||||||||||
| c.4029C>A | H1343Q 2D AIThe SynGAP1 missense variant H1343Q is reported in gnomAD (ID 6‑33451903‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this 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 | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | 6-33451903-C-A | -2.900 | Likely Benign | 0.111 | Likely Benign | Likely Benign | 0.035 | Likely Benign | -1.04 | Neutral | 0.659 | Possibly Damaging | 0.104 | Benign | 4.06 | Benign | 0.00 | Affected | 4.32 | 1 | 0.2126 | 0.3716 | 0 | 3 | -0.3 | -9.01 | ||||||||||||||||||||||||||||||||||||
| c.4029C>G | H1343Q 2D AIThe SynGAP1 missense variant H1343Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are polyPhen2_HumDiv and SIFT. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of predictions, including the high‑accuracy tools, suggest that H1343Q 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 | 0.910643 | Disordered | 0.983646 | Binding | 0.350 | 0.677 | 0.875 | -2.900 | Likely Benign | 0.111 | Likely Benign | Likely Benign | 0.033 | Likely Benign | -1.04 | Neutral | 0.659 | Possibly Damaging | 0.104 | Benign | 4.06 | Benign | 0.00 | Affected | 4.32 | 1 | 0.2126 | 0.3716 | 0 | 3 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||
| c.3211G>A | G1071S 2D AIThe SynGAP1 missense variant G1071S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign impact for G1071S, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | -1.139 | Likely Benign | 0.168 | Likely Benign | Likely Benign | 0.093 | Likely Benign | -1.06 | Neutral | 0.692 | Possibly Damaging | 0.222 | Benign | 4.10 | Benign | 0.28 | Tolerated | 0.2468 | 0.5451 | 1 | 0 | -0.4 | 30.03 | |||||||||||||||||||||||||||||||||||||||
| c.3211G>C | G1071R 2D AIThe SynGAP1 missense variant G1071R is not 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 thus unavailable; Foldetta results are not provided and are therefore unavailable. Overall, more tools predict pathogenicity (5) than benignity (3), and no ClinVar entry contradicts this assessment. **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. | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | -3.052 | Likely Benign | 0.886 | Likely Pathogenic | Ambiguous | 0.135 | Likely Benign | -2.61 | Deleterious | 0.970 | Probably Damaging | 0.728 | Possibly Damaging | 4.06 | Benign | 0.00 | Affected | 0.0980 | 0.4482 | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||||||||
| c.3211G>T | G1071C 2D AIThe SynGAP1 missense variant G1071C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy predictions—supports a benign classification, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | -5.364 | Likely Benign | 0.305 | Likely Benign | Likely Benign | 0.182 | Likely Benign | -2.16 | Neutral | 0.997 | Probably Damaging | 0.889 | Possibly Damaging | 4.01 | Benign | 0.00 | Affected | 0.1323 | 0.4227 | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||||||
| c.3212G>A | G1071D 2D AIThe SynGAP1 missense variant G1071D is not reported 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, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, with no conflict with ClinVar status (which has no entry). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | -4.704 | Likely Benign | 0.866 | Likely Pathogenic | Ambiguous | 0.101 | Likely Benign | -1.92 | Neutral | 0.970 | Probably Damaging | 0.728 | Possibly Damaging | 4.05 | Benign | 0.01 | Affected | 0.1760 | 0.2175 | 1 | -1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||||||
| c.3212G>C | G1071A 2D AIThe SynGAP1 missense variant G1071A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | -1.825 | Likely Benign | 0.229 | Likely Benign | Likely Benign | 0.070 | Likely Benign | -1.34 | Neutral | 0.025 | Benign | 0.022 | Benign | 4.12 | Benign | 0.05 | Affected | 0.3376 | 0.5084 | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3212G>T | G1071V 2D AIThe SynGAP1 missense variant G1071V is catalogued in gnomAD (ID 6‑33443764‑G‑T) but has no ClinVar entry. In silico prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or likely benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, supports a benign interpretation. This prediction does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.919029 | Disordered | 0.983740 | Binding | 0.313 | 0.905 | 0.875 | 6-33443764-G-T | 3 | 1.87e-6 | -2.901 | Likely Benign | 0.300 | Likely Benign | Likely Benign | 0.110 | Likely Benign | -2.42 | Neutral | 0.057 | Benign | 0.022 | Benign | 4.14 | Benign | 0.01 | Affected | 3.77 | 5 | 0.1408 | 0.3634 | -3 | -1 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||||
| c.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.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.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.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.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.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.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.2887C>A | H963N 2D AIThe SynGAP1 missense variant H963N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this 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 | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -8.274 | Likely Pathogenic | 0.099 | Likely Benign | Likely Benign | 0.089 | Likely Benign | -0.21 | Neutral | 0.369 | Benign | 0.120 | Benign | 4.18 | Benign | 0.16 | Tolerated | 0.2094 | 0.3596 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2887C>G | H963D 2D AIThe SynGAP1 missense variant H963D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign; Foldetta results are not available. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign impact for H963D, 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 | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -12.082 | Likely Pathogenic | 0.204 | Likely Benign | Likely Benign | 0.167 | Likely Benign | -0.81 | Neutral | 0.369 | Benign | 0.159 | Benign | 4.16 | Benign | 0.46 | Tolerated | 0.2482 | 0.3023 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2887C>T | H963Y 2D AIThe SynGAP1 missense variant H963Y is catalogued in gnomAD (ID 6‑33443439‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. Only polyPhen‑2 HumDiv predicts a pathogenic effect, while ESM1b remains uncertain. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus likewise 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 points to a benign impact, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | 6-33443439-C-T | 1 | 6.20e-7 | -7.557 | In-Between | 0.158 | Likely Benign | Likely Benign | 0.105 | Likely Benign | -1.13 | Neutral | 0.812 | Possibly Damaging | 0.298 | Benign | 4.09 | Benign | 0.10 | Tolerated | 3.77 | 5 | 0.1627 | 0.4464 | 2 | 0 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||
| c.2888A>C | H963P 2D AIThe SynGAP1 missense variant H963P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only ESM1b predicts a pathogenic outcome, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports benign, and the SGM Consensus also indicates Likely Benign; Foldetta data are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not in conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -8.158 | Likely Pathogenic | 0.074 | Likely Benign | Likely Benign | 0.223 | Likely Benign | -1.10 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.10 | Benign | 0.14 | Tolerated | 0.2101 | 0.4487 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2888A>G | H963R 2D AIThe SynGAP1 missense variant H963R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443440‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only ESM1b predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its status is unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | Uncertain | 1 | 6-33443440-A-G | 8 | 4.96e-6 | -8.952 | Likely Pathogenic | 0.169 | Likely Benign | Likely Benign | 0.081 | Likely Benign | -1.28 | Neutral | 0.001 | Benign | 0.003 | Benign | 4.15 | Benign | 0.24 | Tolerated | 3.77 | 5 | 0.2330 | 0.3380 | 2 | 0 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||||
| c.2888A>T | H963L 2D AIThe SynGAP1 missense variant H963L is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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 the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates benign, and the SGM‑Consensus likewise suggests a benign effect; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for H963L, 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 | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -8.110 | Likely Pathogenic | 0.109 | Likely Benign | Likely Benign | 0.172 | Likely Benign | -1.58 | Neutral | 0.224 | Benign | 0.091 | Benign | 4.13 | Benign | 0.43 | Tolerated | 0.1626 | 0.5680 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2889T>A | H963Q 2D AIThe SynGAP1 missense variant H963Q is not reported 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; the only uncertain result comes from ESM1b. The high‑accuracy consensus methods also support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the evidence overwhelmingly indicates that H963Q 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 | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -7.798 | In-Between | 0.116 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -0.75 | Neutral | 0.411 | Benign | 0.132 | Benign | 4.17 | Benign | 0.29 | Tolerated | 0.2112 | 0.3979 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2889T>G | H963Q 2D AIThe SynGAP1 missense variant H963Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity; the only uncertain result comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise 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 collective evidence strongly supports a benign classification, 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 | 0.991070 | Disordered | 0.983973 | Binding | 0.325 | 0.886 | 0.750 | -7.798 | In-Between | 0.116 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -0.75 | Neutral | 0.411 | Benign | 0.132 | Benign | 4.17 | Benign | 0.29 | Tolerated | 0.2112 | 0.3979 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3271C>A | L1091I 2D AIThe SynGAP1 missense variant L1091I is reported in gnomAD (ID 6‑33443823‑C‑A) but has no ClinVar entry. Across the available in‑silico predictors, every tool classified the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all returned benign scores. No tool predicted pathogenicity, so the pathogenic‑prediction group is empty. High‑accuracy assessments reinforce this benign view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available for this variant. Overall, the computational evidence strongly supports a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.984454 | Binding | 0.376 | 0.889 | 1.000 | 6-33443823-C-A | -4.304 | Likely Benign | 0.273 | Likely Benign | Likely Benign | 0.057 | Likely Benign | -0.66 | Neutral | 0.186 | Benign | 0.055 | Benign | 2.55 | Benign | 0.13 | Tolerated | 3.77 | 5 | 0.1073 | 0.3911 | 2 | 2 | 0.7 | 0.00 | ||||||||||||||||||||||||||||||||||||
| c.3271C>G | L1091V 2D AIThe SynGAP1 missense variant L1091V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the lack of ClinVar evidence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.984454 | Binding | 0.376 | 0.889 | 1.000 | -4.587 | Likely Benign | 0.328 | Likely Benign | Likely Benign | 0.048 | Likely Benign | -0.62 | Neutral | 0.779 | Possibly Damaging | 0.211 | Benign | 2.57 | Benign | 0.08 | Tolerated | 0.1560 | 0.3561 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3272T>A | L1091Q 2D AIThe SynGAP1 missense variant L1091Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. 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) 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 the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.924947 | Disordered | 0.984454 | Binding | 0.376 | 0.889 | 1.000 | -4.381 | Likely Benign | 0.854 | Likely Pathogenic | Ambiguous | 0.155 | Likely Benign | -1.32 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.47 | Pathogenic | 0.02 | Affected | 0.1192 | 0.1514 | -2 | -2 | -7.3 | 14.97 | ||||||||||||||||||||||||||||||||||||||||
| c.3272T>C | L1091P 2D AIThe SynGAP1 missense variant L1091P is listed in gnomAD (ID 6‑33443824‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, leaving it inconclusive. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools (five pathogenic vs three benign) predict a deleterious effect, and the high‑accuracy AlphaMissense‑Optimized score is uncertain. Consequently, the variant is most likely pathogenic based on current predictions, 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. | 0.924947 | Disordered | 0.984454 | Binding | 0.376 | 0.889 | 1.000 | 6-33443824-T-C | -4.139 | Likely Benign | 0.871 | Likely Pathogenic | Ambiguous | 0.180 | Likely Benign | -1.25 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.45 | Pathogenic | 0.04 | Affected | 3.77 | 5 | 0.3199 | 0.1918 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||||
| c.3272T>G | L1091R 2D AIThe SynGAP1 missense variant L1091R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) suggest a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.924947 | Disordered | 0.984454 | Binding | 0.376 | 0.889 | 1.000 | -3.662 | Likely Benign | 0.896 | Likely Pathogenic | Ambiguous | 0.191 | Likely Benign | -1.51 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.47 | Pathogenic | 0.02 | Affected | 0.1274 | 0.1357 | -3 | -2 | -8.3 | 43.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2884C>A | H962N 2D AIThe SynGAP1 missense variant H962N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -8.481 | Likely Pathogenic | 0.098 | Likely Benign | Likely Benign | 0.058 | Likely Benign | -0.61 | Neutral | 0.174 | Benign | 0.045 | Benign | 4.18 | Benign | 0.24 | Tolerated | 0.1957 | 0.3216 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2884C>G | H962D 2D AIThe SynGAP1 missense variant H962D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome. 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 effect. There is no ClinVar entry to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -12.472 | Likely Pathogenic | 0.237 | Likely Benign | Likely Benign | 0.178 | Likely Benign | -1.08 | Neutral | 0.001 | Benign | 0.002 | Benign | 4.20 | Benign | 0.20 | Tolerated | 0.2402 | 0.2643 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2884C>T | H962Y 2D AIThe SynGAP1 missense variant H962Y is not reported 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for H962Y, 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 | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -7.735 | In-Between | 0.167 | Likely Benign | Likely Benign | 0.093 | Likely Benign | -1.27 | Neutral | 0.878 | Possibly Damaging | 0.232 | Benign | 4.12 | Benign | 0.03 | Affected | 0.1741 | 0.4411 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.2885A>C | H962P 2D AIThe SynGAP1 missense variant H962P 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -8.419 | Likely Pathogenic | 0.066 | Likely Benign | Likely Benign | 0.197 | Likely Benign | -0.94 | Neutral | 0.748 | Possibly Damaging | 0.170 | Benign | 4.16 | Benign | 0.07 | Tolerated | 0.2011 | 0.4352 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2885A>G | H962R 2D AIThe SynGAP1 missense variant H962R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the lack of any ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -9.166 | Likely Pathogenic | 0.212 | Likely Benign | Likely Benign | 0.117 | Likely Benign | -1.04 | Neutral | 0.325 | Benign | 0.129 | Benign | 4.18 | Benign | 0.07 | Tolerated | 0.2276 | 0.3337 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2885A>T | H962L 2D AIThe SynGAP1 missense variant H962L is not reported 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for H962L, 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 | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -8.478 | Likely Pathogenic | 0.108 | Likely Benign | Likely Benign | 0.151 | Likely Benign | -1.49 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.15 | Benign | 0.03 | Affected | 0.1738 | 0.5487 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2886C>A | H962Q 2D AIThe SynGAP1 missense variant H962Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b 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). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -8.161 | Likely Pathogenic | 0.130 | Likely Benign | Likely Benign | 0.114 | Likely Benign | -1.04 | Neutral | 0.325 | Benign | 0.045 | Benign | 4.19 | Benign | 0.06 | Tolerated | 0.1943 | 0.3844 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2886C>G | H962Q 2D AIThe SynGAP1 missense variant H962Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome. 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 effect. There is no ClinVar entry to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.991070 | Disordered | 0.984483 | Binding | 0.369 | 0.886 | 0.750 | -8.161 | Likely Pathogenic | 0.130 | Likely Benign | Likely Benign | 0.114 | Likely Benign | -1.04 | Neutral | 0.325 | Benign | 0.045 | Benign | 4.19 | Benign | 0.06 | Tolerated | 0.1943 | 0.3844 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2881C>A | H961N 2D AIThe SynGAP1 missense variant H961N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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 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 H961N 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 | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -8.561 | Likely Pathogenic | 0.096 | Likely Benign | Likely Benign | 0.084 | Likely Benign | -0.32 | Neutral | 0.069 | Benign | 0.036 | Benign | 4.17 | Benign | 0.81 | Tolerated | 0.2074 | 0.3695 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2881C>G | H961D 2D AIThe SynGAP1 missense variant H961D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -12.522 | Likely Pathogenic | 0.224 | Likely Benign | Likely Benign | 0.115 | Likely Benign | -0.98 | Neutral | 0.069 | Benign | 0.036 | Benign | 4.19 | Benign | 0.09 | Tolerated | 0.2487 | 0.2723 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2881C>T | H961Y 2D AIThe SynGAP1 missense variant H961Y is listed in ClinVar with an uncertain significance (ClinVar ID 862637.0) and is present in gnomAD (ID 6‑33443433‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | Conflicting | 2 | 6-33443433-C-T | 3 | 1.86e-6 | -8.051 | Likely Pathogenic | 0.157 | Likely Benign | Likely Benign | 0.102 | Likely Benign | -1.07 | Neutral | 0.716 | Possibly Damaging | 0.147 | Benign | 4.10 | Benign | 0.55 | Tolerated | 3.77 | 5 | 0.1369 | 0.4563 | 0 | 2 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||
| c.2882A>C | H961P 2D AIThe SynGAP1 missense variant H961P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Consequently, the collective evidence indicates that H961P is most likely benign, and this conclusion is not in conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -8.434 | Likely Pathogenic | 0.071 | Likely Benign | Likely Benign | 0.210 | Likely Benign | -0.58 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.15 | Benign | 0.02 | Affected | 0.2061 | 0.4701 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2882A>G | H961R 2D AIThe SynGAP1 missense variant H961R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b. The SGM‑Consensus, which is a 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 assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -9.258 | Likely Pathogenic | 0.189 | Likely Benign | Likely Benign | 0.101 | Likely Benign | -0.90 | Neutral | 0.144 | Benign | 0.078 | Benign | 4.16 | Benign | 0.02 | Affected | 0.2201 | 0.3267 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2882A>T | H961L 2D AIThe SynGAP1 missense variant H961L is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT and ESM1b predict pathogenicity, but these are outliers among the consensus. 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, SGM‑Consensus is benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion 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 | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -8.547 | Likely Pathogenic | 0.109 | Likely Benign | Likely Benign | 0.155 | Likely Benign | -1.21 | Neutral | 0.144 | Benign | 0.078 | Benign | 4.13 | Benign | 0.01 | Affected | 0.1465 | 0.5344 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2883C>A | H961Q 2D AIThe SynGAP1 missense variant H961Q 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. Only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -8.368 | Likely Pathogenic | 0.118 | Likely Benign | Likely Benign | 0.088 | Likely Benign | -0.49 | Neutral | 0.255 | Benign | 0.105 | Benign | 4.17 | Benign | 0.02 | Affected | 0.2022 | 0.3743 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2883C>G | H961Q 2D AIThe SynGAP1 missense variant H961Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT and ESM1b predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority‑benign vote and is reported as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the available predictions indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.989835 | Disordered | 0.984562 | Binding | 0.323 | 0.893 | 0.750 | -8.368 | Likely Pathogenic | 0.118 | Likely Benign | Likely Benign | 0.088 | Likely Benign | -0.49 | Neutral | 0.255 | Benign | 0.105 | Benign | 4.17 | Benign | 0.02 | Affected | 0.2022 | 0.3743 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3214A>C | K1072Q 2D AIThe SynGAP1 missense variant K1072Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.984675 | Binding | 0.307 | 0.907 | 0.750 | -1.631 | Likely Benign | 0.589 | Likely Pathogenic | Likely Benign | 0.081 | Likely Benign | -0.63 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 3.95 | Benign | 0.12 | Tolerated | 0.4465 | 0.1804 | 1 | 1 | 0.4 | -0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3214A>G | K1072E 2D AIThe SynGAP1 missense variant K1072E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments indicate that AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (derived from the same set of predictors) labels it as likely benign. No Foldetta stability analysis is available for this residue. Overall, the majority of tools lean toward a benign effect, but the presence of pathogenic calls from several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of evidence, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.984675 | Binding | 0.307 | 0.907 | 0.750 | -3.889 | Likely Benign | 0.961 | Likely Pathogenic | Likely Pathogenic | 0.105 | Likely Benign | -0.90 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 3.96 | Benign | 0.08 | Tolerated | 0.3636 | 0.1874 | 0 | 1 | 0.4 | 0.94 | |||||||||||||||||||||||||||||||||||||||
| c.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.3215A>G | K1072R 2D AIThe SynGAP1 missense variant K1072R is reported in gnomAD (ID 6‑33443767‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. When predictions are grouped by consensus, the benign group contains seven tools, whereas the pathogenic group contains two. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability data are available, so folding‑stability evidence is unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.984675 | Binding | 0.307 | 0.907 | 0.750 | 6-33443767-A-G | 1 | 6.23e-7 | -2.458 | Likely Benign | 0.100 | Likely Benign | Likely Benign | 0.116 | Likely Benign | -0.15 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 4.16 | Benign | 0.88 | Tolerated | 3.77 | 5 | 0.4655 | 0.2061 | 2 | 3 | -0.6 | 28.01 | ||||||||||||||||||||||||||||||||||
| 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.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.2800A>C | M934L 2D  AIThe SynGAP1 missense variant M934L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign impact, and this is consistent with the lack of a ClinVar classification—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -2.482 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.093 | Likely Benign | -0.73 | Neutral | 0.002 | Benign | 0.002 | Benign | 3.03 | Benign | 0.68 | Tolerated | 0.2004 | 0.4051 | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.2800A>G | M934V 2D  AIThe SynGAP1 missense variant M934V is listed in gnomAD (ID 6‑33443352‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, 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 classify the change as benign or likely benign. Only FATHMM predicts a pathogenic outcome, representing a single dissenting signal. High‑accuracy assessments confirm the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that M934V 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 | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | 6-33443352-A-G | 1 | 6.20e-7 | -3.286 | Likely Benign | 0.218 | Likely Benign | Likely Benign | 0.119 | Likely Benign | -2.06 | Neutral | 0.166 | Benign | 0.101 | Benign | 2.47 | Pathogenic | 0.39 | Tolerated | 3.77 | 5 | 0.3464 | 0.3276 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||||||||||||||
| c.2800A>T | M934L 2D AIThe SynGAP1 missense variant M934L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, 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 | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -2.482 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.093 | Likely Benign | -0.73 | Neutral | 0.002 | Benign | 0.002 | Benign | 3.03 | Benign | 0.68 | Tolerated | 0.2004 | 0.4051 | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.2801T>A | M934K 2D  AIThe SynGAP1 missense variant M934K is not 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 ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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) is unavailable for this variant. Overall, the balance of evidence from the majority of tools points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -2.457 | Likely Benign | 0.816 | Likely Pathogenic | Ambiguous | 0.333 | Likely Benign | -3.66 | Deleterious | 0.929 | Possibly Damaging | 0.521 | Possibly Damaging | 2.38 | Pathogenic | 0.13 | Tolerated | 0.1828 | 0.1262 | 0 | -1 | -5.8 | -3.02 | |||||||||||||||||||||||||||||||||||||||
| c.2801T>C | M934T 2D  AIThe SynGAP1 missense variant M934T is not 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, SIFT, and ESM1b, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Based on the majority of predictions and the consensus call, the variant is most likely pathogenic; 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 | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -2.579 | Likely Benign | 0.823 | Likely Pathogenic | Ambiguous | 0.270 | Likely Benign | -3.33 | Deleterious | 0.811 | Possibly Damaging | 0.424 | Benign | 2.39 | Pathogenic | 0.19 | Tolerated | 0.2331 | 0.2267 | -1 | -1 | -2.6 | -30.09 | |||||||||||||||||||||||||||||||||||||||
| c.2801T>G | M934R 2D  AISynGAP1 missense variant M934R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence 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. | Likely Pathogenic | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -1.854 | Likely Benign | 0.771 | Likely Pathogenic | Likely Benign | 0.322 | Likely Benign | -3.54 | Deleterious | 0.969 | Probably Damaging | 0.624 | Possibly Damaging | 2.37 | Pathogenic | 0.11 | Tolerated | 0.1902 | 0.1243 | 0 | -1 | -6.4 | 24.99 | |||||||||||||||||||||||||||||||||||||||
| c.2802G>A | M934I 2D  AIThe SynGAP1 missense variant M934I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. Overall, the majority of evidence (seven benign versus two pathogenic predictions) indicates that M934I 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. | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -4.582 | Likely Benign | 0.757 | Likely Pathogenic | Likely Benign | 0.086 | Likely Benign | -1.78 | Neutral | 0.316 | Benign | 0.101 | Benign | 2.49 | Pathogenic | 0.27 | Tolerated | 0.1686 | 0.3100 | 2 | 1 | 2.6 | -18.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2802G>C | M934I 2D AIThe SynGAP1 missense variant M934I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. Overall, the majority of evidence (seven benign versus two pathogenic predictions) indicates that M934I 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. | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -4.582 | Likely Benign | 0.757 | Likely Pathogenic | Likely Benign | 0.085 | Likely Benign | -1.78 | Neutral | 0.316 | Benign | 0.101 | Benign | 2.49 | Pathogenic | 0.27 | Tolerated | 0.1686 | 0.3100 | 2 | 1 | 2.6 | -18.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2802G>T | M934I 2D AIThe SynGAP1 missense variant M934I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. Overall, the majority of evidence (seven benign versus two pathogenic predictions) indicates that M934I 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. | 0.762850 | Disordered | 0.984677 | Binding | 0.290 | 0.867 | 0.625 | -4.582 | Likely Benign | 0.757 | Likely Pathogenic | Likely Benign | 0.085 | Likely Benign | -1.78 | Neutral | 0.316 | Benign | 0.101 | Benign | 2.49 | Pathogenic | 0.27 | Tolerated | 0.1686 | 0.3100 | 2 | 1 | 2.6 | -18.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2779T>A | F927I 2D AIThe SynGAP1 missense variant F927I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools indicates that F927I 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 | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -4.793 | Likely Benign | 0.997 | Likely Pathogenic | Likely Pathogenic | 0.370 | Likely Benign | -4.50 | Deleterious | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 1.34 | Pathogenic | 0.00 | Affected | 0.2255 | 0.1238 | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2779T>C | F927L 2D AIThe SynGAP1 missense variant F927L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that F927L 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 | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -4.227 | Likely Benign | 1.000 | Likely Pathogenic | Likely Pathogenic | 0.317 | Likely Benign | -4.48 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.39 | Pathogenic | 0.00 | Affected | 0.2214 | 0.2209 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2779T>G | F927V 2D AIThe SynGAP1 missense variant F927V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, 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 effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable and therefore not considered. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools indicates that the variant is most likely pathogenic, with no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -4.919 | Likely Benign | 0.996 | Likely Pathogenic | Likely Pathogenic | 0.470 | Likely Benign | -5.21 | Deleterious | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 1.34 | Pathogenic | 0.00 | Affected | 0.2207 | 0.1206 | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||||||
| c.2780T>A | F927Y 2D AIThe SynGAP1 missense variant F927Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic interpretation. 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. | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -5.244 | Likely Benign | 0.954 | Likely Pathogenic | Ambiguous | 0.291 | Likely Benign | -2.29 | Neutral | 0.997 | Probably Damaging | 0.987 | Probably Damaging | 1.40 | Pathogenic | 0.00 | Affected | 0.1551 | 0.1518 | 7 | 3 | -4.1 | 16.00 | ||||||||||||||||||||||||||||||||||||||||
| c.2780T>C | F927S 2D AIThe SynGAP1 missense variant F927S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, 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). AlphaMissense‑Optimized alone predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the preponderance of pathogenic predictions—including the high‑accuracy consensus—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 | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -5.480 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.481 | Likely Benign | -5.68 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.32 | Pathogenic | 0.00 | Affected | 0.4748 | 0.0591 | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||||||
| c.2780T>G | F927C 2D AIThe SynGAP1 missense variant F927C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are not available. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -8.298 | Likely Pathogenic | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.523 | Likely Pathogenic | -6.02 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 1.31 | Pathogenic | 0.00 | Affected | 0.2921 | 0.1291 | -4 | -2 | -0.3 | -44.04 | |||||||||||||||||||||||||||||||||||||||
| c.2781C>A | F927L 2D AIThe SynGAP1 missense variant F927L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that F927L 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 | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -4.227 | Likely Benign | 1.000 | Likely Pathogenic | Likely Pathogenic | 0.296 | Likely Benign | -4.48 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.39 | Pathogenic | 0.00 | Affected | 0.2214 | 0.2209 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2781C>G | F927L 2D AIThe SynGAP1 missense variant F927L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.529623 | Disordered | 0.985043 | Binding | 0.324 | 0.854 | 0.250 | -4.227 | Likely Benign | 1.000 | Likely Pathogenic | Likely Pathogenic | 0.296 | Likely Benign | -4.48 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.39 | Pathogenic | 0.00 | Affected | 0.2214 | 0.2209 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.3274T>A | L1092M 2D AIThe SynGAP1 missense variant L1092M is not reported in ClinVar and has no entries in gnomAD, indicating it has not been catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy predictions from AlphaMissense‑Optimized and the SGM‑Consensus both support a benign outcome, whereas the absence of a Foldetta result precludes a stability‑based conclusion. Overall, the majority of evidence points to a benign effect for the variant, 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 | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | -5.348 | Likely Benign | 0.383 | Ambiguous | Likely Benign | 0.083 | Likely Benign | -0.15 | Neutral | 0.986 | Probably Damaging | 0.875 | Possibly Damaging | 2.66 | Benign | 0.21 | Tolerated | 0.0919 | 0.4479 | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3274T>G | L1092V 2D AIThe SynGAP1 missense variant L1092V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | -4.906 | Likely Benign | 0.451 | Ambiguous | Likely Benign | 0.034 | Likely Benign | -0.36 | Neutral | 0.051 | Benign | 0.037 | Benign | 2.79 | Benign | 0.37 | Tolerated | 0.1658 | 0.3912 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3275T>C | L1092S 2D AIThe SynGAP1 missense variant L1092S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | -3.649 | Likely Benign | 0.900 | Likely Pathogenic | Ambiguous | 0.121 | Likely Benign | -0.42 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.68 | Benign | 0.25 | Tolerated | 0.3086 | 0.1119 | -3 | -2 | -4.6 | -26.08 | |||||||||||||||||||||||||||||||||||||||
| c.3275T>G | L1092W 2D AIThe SynGAP1 missense variant L1092W 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, 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 assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta is unavailable. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus leans toward a benign interpretation. Thus, the variant is most likely benign based on the most reliable predictions, 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. | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | -7.014 | In-Between | 0.804 | Likely Pathogenic | Ambiguous | 0.120 | Likely Benign | -2.00 | Neutral | 0.999 | Probably Damaging | 0.968 | Probably Damaging | 2.58 | Benign | 0.03 | Affected | 0.0787 | 0.4033 | -2 | -2 | -4.7 | 73.05 | ||||||||||||||||||||||||||||||||||||||||
| c.3276G>C | L1092F 2D AIThe SynGAP1 missense variant L1092F is reported in gnomAD (6‑33443828‑G‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | 6-33443828-G-C | 1 | 6.40e-7 | -5.010 | Likely Benign | 0.623 | Likely Pathogenic | Likely Benign | 0.067 | Likely Benign | -1.40 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.63 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.0772 | 0.4060 | 0 | 2 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||
| c.3276G>T | L1092F 2D AIThe SynGAP1 missense variant L1092F is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools show a split: benign calls from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also leans benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.924947 | Disordered | 0.985431 | Binding | 0.385 | 0.890 | 1.000 | -5.010 | Likely Benign | 0.623 | Likely Pathogenic | Likely Benign | 0.067 | Likely Benign | -1.40 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.63 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0.0772 | 0.4060 | 0 | 2 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||||
| c.3217T>A | S1073T 2D AIThe SynGAP1 missense variant S1073T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.916840 | Disordered | 0.985818 | Binding | 0.313 | 0.905 | 0.750 | -5.203 | Likely Benign | 0.169 | Likely Benign | Likely Benign | 0.161 | Likely Benign | -0.26 | Neutral | 0.025 | Benign | 0.026 | Benign | 4.06 | Benign | 0.55 | Tolerated | 0.1696 | 0.6509 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| 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.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.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.3109A>C | I1037L 2D AIThe SynGAP1 missense variant I1037L is not reported in ClinVar and is absent from gnomAD, indicating no known clinical or population evidence. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, and the only uncertain call comes from AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise 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 consensus of available predictions indicates that I1037L 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 | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -2.563 | Likely Benign | 0.448 | Ambiguous | Likely Benign | 0.074 | Likely Benign | -0.46 | Neutral | 0.421 | Benign | 0.128 | Benign | 2.82 | Benign | 0.81 | Tolerated | 0.0939 | 0.4302 | 2 | 2 | -0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.3109A>G | I1037V 2D AIThe SynGAP1 missense variant I1037V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that I1037V is most likely benign, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -2.326 | Likely Benign | 0.461 | Ambiguous | Likely Benign | 0.085 | Likely Benign | -0.09 | Neutral | 0.421 | Benign | 0.128 | Benign | 2.76 | Benign | 0.93 | Tolerated | 0.1229 | 0.3985 | 4 | 3 | -0.3 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3109A>T | I1037F 2D AIThe SynGAP1 missense variant I1037F is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in‑silico predictors shows a split: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy tools further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment is consistent with the absence of a ClinVar pathogenic claim. Thus, the variant is most likely benign, and this conclusion does not contradict ClinVar, which has no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -3.517 | Likely Benign | 0.653 | Likely Pathogenic | Likely Benign | 0.115 | Likely Benign | -0.97 | Neutral | 0.977 | Probably Damaging | 0.632 | Possibly Damaging | 2.71 | Benign | 0.16 | Tolerated | 0.0653 | 0.3722 | 1 | 0 | -1.7 | 34.02 | |||||||||||||||||||||||||||||||||||||||
| c.3110T>A | I1037N 2D AIThe SynGAP1 missense variant I1037N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a Likely Benign classification, while AlphaMissense‑Optimized remains uncertain. Foldetta stability analysis is 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 | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -3.955 | Likely Benign | 0.832 | Likely Pathogenic | Ambiguous | 0.131 | Likely Benign | 1.56 | Neutral | 0.666 | Possibly Damaging | 0.211 | Benign | 2.81 | Benign | 0.34 | Tolerated | 0.1022 | 0.1140 | -2 | -3 | -8.0 | 0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3110T>C | I1037T 2D AIThe SynGAP1 missense variant I1037T is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443662‑T‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports 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 predictions (seven benign vs. two pathogenic) indicate that the variant is most likely benign, 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. | Likely Benign | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | 6-33443662-T-C | 1 | 6.21e-7 | -2.565 | Likely Benign | 0.973 | Likely Pathogenic | Likely Pathogenic | 0.066 | Likely Benign | 0.40 | Neutral | 0.292 | Benign | 0.110 | Benign | 2.79 | Benign | 0.34 | Tolerated | 3.77 | 5 | 0.1071 | 0.2175 | -1 | 0 | -5.2 | -12.05 | ||||||||||||||||||||||||||||||||||
| c.3110T>G | I1037S 2D AIThe SynGAP1 missense variant I1037S is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Based on the overall consensus of the majority of tools, 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 | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -2.247 | Likely Benign | 0.935 | Likely Pathogenic | Ambiguous | 0.120 | Likely Benign | 0.43 | Neutral | 0.032 | Benign | 0.017 | Benign | 2.83 | Benign | 0.27 | Tolerated | 0.2634 | 0.1110 | -1 | -2 | -5.3 | -26.08 | |||||||||||||||||||||||||||||||||||||||
| c.3111C>G | I1037M 2D AIThe SynGAP1 missense variant I1037M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only two tools, polyPhen‑2 HumDiv and polyPhen‑2 HumVar, predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.939629 | Disordered | 0.986140 | Binding | 0.309 | 0.774 | 0.625 | -3.849 | Likely Benign | 0.333 | Likely Benign | Likely Benign | 0.093 | Likely Benign | -0.40 | Neutral | 0.977 | Probably Damaging | 0.721 | Possibly Damaging | 2.71 | Benign | 0.18 | Tolerated | 0.0775 | 0.3885 | 2 | 1 | -2.6 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.2782C>A | Q928K 2D AIThe SynGAP1 missense variant Q928K has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. High‑accuracy evidence therefore consists of an uncertain AlphaMissense‑Optimized score, a Likely Pathogenic SGM‑Consensus, and an unavailable Foldetta prediction. Overall, the majority of tools predict pathogenicity, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -4.941 | Likely Benign | 0.897 | Likely Pathogenic | Ambiguous | 0.259 | Likely Benign | -2.80 | Deleterious | 0.985 | Probably Damaging | 0.981 | Probably Damaging | 1.60 | Pathogenic | 0.00 | Affected | 0.1728 | 0.5306 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.2782C>G | Q928E 2D AIThe SynGAP1 missense variant Q928E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -5.168 | Likely Benign | 0.590 | Likely Pathogenic | Likely Benign | 0.283 | Likely Benign | -2.06 | Neutral | 0.985 | Probably Damaging | 0.981 | Probably Damaging | 1.58 | Pathogenic | 0.00 | Affected | 0.1368 | 0.3477 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||||||||||||
| c.2783A>C | Q928P 2D AIThe SynGAP1 missense variant Q928P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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. Based on the preponderance of pathogenic predictions and the SGM‑Consensus designation, the variant is most likely pathogenic; 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 | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -6.275 | Likely Benign | 0.832 | Likely Pathogenic | Ambiguous | 0.441 | Likely Benign | -4.28 | Deleterious | 0.998 | Probably Damaging | 0.995 | Probably Damaging | 1.54 | Pathogenic | 0.00 | Affected | 0.2016 | 0.5768 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.2783A>G | Q928R 2D AIThe SynGAP1 missense variant Q928R is listed in gnomAD (ID 6‑33443335‑A‑G) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta stability) data are available. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no contradictory evidence from ClinVar. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | 6-33443335-A-G | 1 | 6.20e-7 | -4.089 | Likely Benign | 0.826 | Likely Pathogenic | Ambiguous | 0.290 | Likely Benign | -2.91 | Deleterious | 0.994 | Probably Damaging | 0.988 | Probably Damaging | 1.58 | Pathogenic | 0.00 | Affected | 4.32 | 4 | 0.1357 | 0.3453 | 1 | 1 | -1.0 | 28.06 | ||||||||||||||||||||||||||||||||||
| c.2783A>T | Q928L 2D AIThe SynGAP1 missense variant Q928L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion is not contradicted by 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 | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -6.237 | Likely Benign | 0.919 | Likely Pathogenic | Ambiguous | 0.373 | Likely Benign | -4.57 | Deleterious | 0.994 | Probably Damaging | 0.988 | Probably Damaging | 1.56 | Pathogenic | 0.00 | Affected | 0.0757 | 0.6091 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.2784G>C | Q928H 2D AIThe SynGAP1 missense variant Q928H 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 ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion 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 | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -4.358 | Likely Benign | 0.929 | Likely Pathogenic | Ambiguous | 0.329 | Likely Benign | -3.65 | Deleterious | 0.998 | Probably Damaging | 0.996 | Probably Damaging | 1.54 | Pathogenic | 0.00 | Affected | 0.1389 | 0.4811 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2784G>T | Q928H 2D AIThe SynGAP1 missense variant Q928H 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 ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion 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 | 0.497853 | Structured | 0.986260 | Binding | 0.324 | 0.852 | 0.250 | -4.358 | Likely Benign | 0.929 | Likely Pathogenic | Ambiguous | 0.330 | Likely Benign | -3.65 | Deleterious | 0.998 | Probably Damaging | 0.996 | Probably Damaging | 1.54 | Pathogenic | 0.00 | Affected | 0.1389 | 0.4811 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2785A>C | N929H 2D AIThe SynGAP1 missense variant N929H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain, and Foldetta results are unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. With no conflicting ClinVar annotation, the collective evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -7.070 | In-Between | 0.967 | Likely Pathogenic | Likely Pathogenic | 0.342 | Likely Benign | -3.52 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.45 | Pathogenic | 0.00 | Affected | 0.1507 | 0.7659 | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||||||
| c.2785A>G | N929D 2D AIThe SynGAP1 missense variant N929D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which reports “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are 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 present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -6.856 | Likely Benign | 0.992 | Likely Pathogenic | Likely Pathogenic | 0.365 | Likely Benign | -3.86 | Deleterious | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 1.49 | Pathogenic | 0.00 | Affected | 0.1991 | 0.4605 | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.2785A>T | N929Y 2D AIThe SynGAP1 missense variant N929Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL predicts benign, whereas the remaining eleven predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -10.327 | Likely Pathogenic | 0.982 | Likely Pathogenic | Likely Pathogenic | 0.391 | Likely Benign | -6.02 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.45 | Pathogenic | 0.00 | Affected | 0.0656 | 0.6489 | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||||||
| c.2786A>C | N929T 2D AIThe SynGAP1 missense variant N929T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability analysis is available. Taken together, the overwhelming majority of evidence supports a pathogenic classification for N929T, and this conclusion is consistent with the absence of a ClinVar entry (i.e., there is no conflicting ClinVar status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -9.245 | Likely Pathogenic | 0.987 | Likely Pathogenic | Likely Pathogenic | 0.257 | Likely Benign | -4.68 | Deleterious | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 1.47 | Pathogenic | 0.00 | Affected | 0.1469 | 0.8140 | 0 | 0 | 2.8 | -13.00 | |||||||||||||||||||||||||||||||||||||||
| c.2786A>G | N929S 2D AIThe SynGAP1 missense variant N929S is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a consensus toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, while REVEL uniquely predicts a benign outcome. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a damaging interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta data are unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for N929S. This conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -7.100 | In-Between | 0.948 | Likely Pathogenic | Ambiguous | 0.249 | Likely Benign | -3.89 | Deleterious | 0.999 | Probably Damaging | 0.992 | Probably Damaging | 1.48 | Pathogenic | 0.00 | Affected | 0.4117 | 0.7639 | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||||||
| c.2786A>T | N929I 2D AIThe SynGAP1 missense variant N929I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining eight tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus result is consistent. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -11.799 | Likely Pathogenic | 0.995 | Likely Pathogenic | Likely Pathogenic | 0.297 | Likely Benign | -6.82 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.45 | Pathogenic | 0.00 | Affected | 0.0780 | 0.6486 | -2 | -3 | 8.0 | -0.94 | |||||||||||||||||||||||||||||||||||||||
| c.2787C>A | N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -10.041 | Likely Pathogenic | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.182 | Likely Benign | -4.35 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.48 | Pathogenic | 0.00 | Affected | 0.2098 | 0.6046 | 1 | 0 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||||
| c.2787C>G | N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.557691 | Disordered | 0.986867 | Binding | 0.321 | 0.851 | 0.375 | -10.041 | Likely Pathogenic | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.182 | Likely Benign | -4.35 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.48 | Pathogenic | 0.00 | Affected | 0.2098 | 0.6046 | 1 | 0 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||||
| c.3064C>A | L1022I 2D AIThe SynGAP1 missense variant L1022I is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | -4.624 | Likely Benign | 0.166 | Likely Benign | Likely Benign | 0.025 | Likely Benign | -0.91 | Neutral | 0.114 | Benign | 0.072 | Benign | 2.58 | Benign | 0.11 | Tolerated | 0.1081 | 0.4395 | 2 | 2 | 0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.3064C>G | L1022V 2D AIThe SynGAP1 missense variant L1022V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, creating a single discordant prediction. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | -3.957 | Likely Benign | 0.174 | Likely Benign | Likely Benign | 0.035 | Likely Benign | -1.22 | Neutral | 0.664 | Possibly Damaging | 0.260 | Benign | 2.66 | Benign | 0.07 | Tolerated | 0.1702 | 0.4045 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3064C>T | L1022F 2D AIThe SynGAP1 missense variant L1022F is reported in gnomAD (variant ID 6‑33443616‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | 6-33443616-C-T | 2 | 1.24e-6 | -5.035 | Likely Benign | 0.351 | Ambiguous | Likely Benign | 0.072 | Likely Benign | -1.84 | Neutral | 0.971 | Probably Damaging | 0.801 | Possibly Damaging | 2.51 | Benign | 0.07 | Tolerated | 3.77 | 5 | 0.0730 | 0.4231 | 0 | 2 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||
| c.3065T>A | L1022H 2D AIThe SynGAP1 missense variant L1022H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while 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 inconclusive. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of conventional predictors lean toward pathogenicity, whereas the single high‑accuracy tool predicts benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the 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. | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | -2.473 | Likely Benign | 0.589 | Likely Pathogenic | Likely Benign | 0.140 | Likely Benign | -2.21 | Neutral | 0.999 | Probably Damaging | 0.944 | Probably Damaging | 2.49 | Pathogenic | 0.00 | Affected | 0.1165 | 0.1313 | -2 | -3 | -7.0 | 23.98 | ||||||||||||||||||||||||||||||||||||||||
| c.3065T>C | L1022P 2D AIThe SynGAP1 missense variant L1022P 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, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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, two benign), and Foldetta data are unavailable. Overall, the balance of evidence favors a pathogenic interpretation, and this assessment does not conflict with ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | -2.532 | Likely Benign | 0.643 | Likely Pathogenic | Likely Benign | 0.177 | Likely Benign | -2.22 | Neutral | 0.995 | Probably Damaging | 0.925 | Probably Damaging | 2.49 | Pathogenic | 0.01 | Affected | 0.3332 | 0.1589 | -3 | -3 | -5.4 | -16.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3065T>G | L1022R 2D AIThe SynGAP1 missense variant L1022R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L1022R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.859585 | Disordered | 0.986981 | Binding | 0.339 | 0.752 | 0.500 | -2.875 | Likely Benign | 0.659 | Likely Pathogenic | Likely Benign | 0.183 | Likely Benign | -1.96 | Neutral | 0.986 | Probably Damaging | 0.894 | Possibly Damaging | 2.51 | Benign | 0.01 | Affected | 0.1279 | 0.1387 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.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.3232G>C | V1078L 2D  AIThe SynGAP1 missense variant V1078L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective evidence strongly suggests that V1078L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.882776 | Disordered | 0.986989 | Binding | 0.294 | 0.898 | 0.750 | -2.547 | Likely Benign | 0.523 | Ambiguous | Likely Benign | 0.091 | Likely Benign | -0.16 | Neutral | 0.451 | Benign | 0.209 | Benign | 4.13 | Benign | 0.56 | Tolerated | 0.0889 | 0.5349 | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| 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.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.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.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.3220C>A | Q1074K 2D AIThe SynGAP1 missense variant Q1074K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | -6.162 | Likely Benign | 0.712 | Likely Pathogenic | Likely Benign | 0.110 | Likely Benign | -0.88 | Neutral | 0.011 | Benign | 0.006 | Benign | 2.75 | Benign | 0.36 | Tolerated | 0.1865 | 0.4600 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3220C>G | Q1074E 2D AIThe SynGAP1 missense variant Q1074E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions strongly suggests 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 | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | -2.815 | Likely Benign | 0.419 | Ambiguous | Likely Benign | 0.096 | Likely Benign | -0.79 | Neutral | 0.264 | Benign | 0.103 | Benign | 2.79 | Benign | 0.24 | Tolerated | 0.1386 | 0.2856 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3221A>C | Q1074P 2D AIThe SynGAP1 missense variant Q1074P is listed in gnomAD (ID 6‑33443773‑A‑C) 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 report benign or tolerated. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single outlier. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | 6-33443773-A-C | 1 | 6.23e-7 | -4.259 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.188 | Likely Benign | 0.52 | Neutral | 0.925 | Possibly Damaging | 0.432 | Benign | 2.66 | Benign | 0.13 | Tolerated | 3.77 | 5 | 0.2046 | 0.5784 | -1 | 0 | 1.9 | -31.01 | ||||||||||||||||||||||||||||||||||
| c.3221A>G | Q1074R 2D AIThe SynGAP1 missense variant Q1074R is listed in gnomAD (ID 6‑33443773‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none reported). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | 6-33443773-A-G | -5.710 | Likely Benign | 0.594 | Likely Pathogenic | Likely Benign | 0.124 | Likely Benign | -0.54 | Neutral | 0.292 | Benign | 0.157 | Benign | 2.70 | Benign | 0.28 | Tolerated | 3.77 | 5 | 0.1523 | 0.2643 | 1 | 1 | -1.0 | 28.06 | ||||||||||||||||||||||||||||||||||||
| c.3221A>T | Q1074L 2D AIThe SynGAP1 missense variant Q1074L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | -3.561 | Likely Benign | 0.259 | Likely Benign | Likely Benign | 0.118 | Likely Benign | -1.29 | Neutral | 0.625 | Possibly Damaging | 0.266 | Benign | 2.68 | Benign | 1.00 | Tolerated | 0.0840 | 0.6293 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3222G>C | Q1074H 2D AIThe SynGAP1 missense variant Q1074H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, and the only uncertain call comes from AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of 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 | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | -5.051 | Likely Benign | 0.381 | Ambiguous | Likely Benign | 0.053 | Likely Benign | -0.12 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.67 | Benign | 0.07 | Tolerated | 0.1436 | 0.4407 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3222G>T | Q1074H 2D AIThe SynGAP1 missense variant Q1074H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, and the only uncertain call comes from AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of 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 | 0.930790 | Disordered | 0.987006 | Binding | 0.339 | 0.897 | 0.750 | -5.051 | Likely Benign | 0.381 | Ambiguous | Likely Benign | 0.053 | Likely Benign | -0.12 | Neutral | 0.006 | Benign | 0.008 | Benign | 2.67 | Benign | 0.07 | Tolerated | 0.1436 | 0.4407 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2797C>A | H933N 2D AIThe SynGAP1 missense variant H933N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta are unavailable. Overall, five tools predict pathogenicity versus four predicting benignity, suggesting the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -4.333 | Likely Benign | 0.226 | Likely Benign | Likely Benign | 0.261 | Likely Benign | -3.65 | Deleterious | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.39 | Pathogenic | 0.04 | Affected | 0.1897 | 0.3439 | 2 | 1 | -0.3 | -23.04 | ||||||||||||||||||||||||||||||||||||||||
| c.2797C>G | H933D 2D AIThe SynGAP1 missense variant H933D is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic, matching the majority of individual scores. AlphaMissense‑Optimized returns an Uncertain result, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a pathogenic effect for H933D. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -2.888 | Likely Benign | 0.798 | Likely Pathogenic | Ambiguous | 0.320 | Likely Benign | -4.70 | Deleterious | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.40 | Pathogenic | 0.04 | Affected | 0.2481 | 0.2717 | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||||||
| c.2797C>T | H933Y 2D AIThe SynGAP1 H933Y 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, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic prediction. Foldetta results are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign predictions) points to a pathogenic impact for H933Y. 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. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -3.952 | Likely Benign | 0.525 | Ambiguous | Likely Benign | 0.314 | Likely Benign | -3.49 | Deleterious | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.36 | Pathogenic | 0.01 | Affected | 0.0968 | 0.4815 | 0 | 2 | 1.9 | 26.03 | ||||||||||||||||||||||||||||||||||||||||
| c.2798A>C | H933P 2D AIThe SynGAP1 missense variant H933P 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 ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, six tools predict pathogenicity versus three predicting benign, and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. 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. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -3.890 | Likely Benign | 0.332 | Likely Benign | Likely Benign | 0.508 | Likely Pathogenic | -5.39 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.36 | Pathogenic | 0.02 | Affected | 0.1821 | 0.4400 | 0 | -2 | 1.6 | -40.02 | ||||||||||||||||||||||||||||||||||||||||
| c.2798A>G | H933R 2D AIThe SynGAP1 missense variant H933R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -4.410 | Likely Benign | 0.650 | Likely Pathogenic | Likely Benign | 0.393 | Likely Benign | -3.84 | Deleterious | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.43 | Pathogenic | 0.06 | Tolerated | 0.2074 | 0.2922 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.2798A>T | H933L 2D AIThe SynGAP1 H933L 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 AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. 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. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -0.858 | Likely Benign | 0.470 | Ambiguous | Likely Benign | 0.388 | Likely Benign | -6.26 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.38 | Pathogenic | 0.02 | Affected | 0.1003 | 0.5749 | -2 | -3 | 7.0 | -23.98 | ||||||||||||||||||||||||||||||||||||||||
| c.2799C>A | H933Q 2D AIThe SynGAP1 missense variant H933Q has no ClinVar record and is not present in gnomAD. 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, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (two benign versus one pathogenic vote). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is unavailable for this variant. Overall, the preponderance of 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. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -3.042 | Likely Benign | 0.410 | Ambiguous | Likely Benign | 0.211 | Likely Benign | -2.98 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.54 | Benign | 0.53 | Tolerated | 0.1654 | 0.3938 | 3 | 0 | -0.3 | -9.01 | ||||||||||||||||||||||||||||||||||||||||
| c.2799C>G | H933Q 2D AIThe SynGAP1 H933Q 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, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.987531 | Binding | 0.305 | 0.862 | 0.625 | -3.042 | Likely Benign | 0.410 | Ambiguous | Likely Benign | 0.210 | Likely Benign | -2.98 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.54 | Benign | 0.53 | Tolerated | 0.1654 | 0.3938 | 3 | 0 | -0.3 | -9.01 | ||||||||||||||||||||||||||||||||||||||||
| c.3106C>A | Q1036K 2D AIThe SynGAP1 missense variant Q1036K is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -3.757 | Likely Benign | 0.646 | Likely Pathogenic | Likely Benign | 0.079 | Likely Benign | -1.72 | Neutral | 0.011 | Benign | 0.005 | Benign | 2.58 | Benign | 0.05 | Affected | 0.2096 | 0.5220 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3106C>G | Q1036E 2D AIThe SynGAP1 missense variant Q1036E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. When predictions are grouped by consensus, the benign group contains nine tools, while the pathogenic group contains one (SIFT). High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable, so they do not influence the assessment. Overall, the evidence strongly suggests 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 | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -3.797 | Likely Benign | 0.313 | Likely Benign | Likely Benign | 0.056 | Likely Benign | -1.22 | Neutral | 0.264 | Benign | 0.062 | Benign | 2.59 | Benign | 0.03 | Affected | 0.1629 | 0.3484 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3107A>C | Q1036P 2D AIThe SynGAP1 missense variant Q1036P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and the consensus score indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -2.491 | Likely Benign | 0.135 | Likely Benign | Likely Benign | 0.104 | Likely Benign | -2.00 | Neutral | 0.802 | Possibly Damaging | 0.238 | Benign | 2.57 | Benign | 0.01 | Affected | 0.2018 | 0.5564 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3107A>G | Q1036R 2D AIThe SynGAP1 missense variant Q1036R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from 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 four high‑accuracy tools) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective evidence points to a benign effect for Q1036R, 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 | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -3.816 | Likely Benign | 0.596 | Likely Pathogenic | Likely Benign | 0.083 | Likely Benign | -1.32 | Neutral | 0.292 | Benign | 0.071 | Benign | 2.54 | Benign | 0.04 | Affected | 0.1710 | 0.3071 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3107A>T | Q1036L 2D AIThe SynGAP1 missense variant Q1036L is not 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, 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 favors a benign outcome, with two benign votes versus one pathogenic and 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 evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -4.389 | Likely Benign | 0.435 | Ambiguous | Likely Benign | 0.092 | Likely Benign | -2.92 | Deleterious | 0.152 | Benign | 0.045 | Benign | 2.52 | Benign | 0.01 | Affected | 0.1069 | 0.5996 | -2 | -2 | 7.3 | -14.97 | ||||||||||||||||||||||||||||||||||||||||
| c.3108G>C | Q1036H 2D AIThe SynGAP1 missense variant Q1036H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote 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. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | -4.189 | Likely Benign | 0.536 | Ambiguous | Likely Benign | 0.065 | Likely Benign | -1.18 | Neutral | 0.977 | Probably Damaging | 0.615 | Possibly Damaging | 2.50 | Benign | 0.29 | Tolerated | 3.77 | 5 | 0.1641 | 0.4835 | 0 | 3 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||
| c.3108G>T | Q1036H 2D AIThe SynGAP1 missense variant Q1036H is listed in gnomAD (ID 6‑33443660‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default 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 are missing. Overall, the majority of reliable predictors indicate a benign impact, 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 | 0.948786 | Disordered | 0.987955 | Binding | 0.275 | 0.765 | 0.625 | 6-33443660-G-T | 1 | 6.20e-7 | -4.189 | Likely Benign | 0.536 | Ambiguous | Likely Benign | 0.065 | Likely Benign | -1.18 | Neutral | 0.977 | Probably Damaging | 0.615 | Possibly Damaging | 2.50 | Benign | 0.29 | Tolerated | 3.77 | 5 | 0.1641 | 0.4835 | 0 | 3 | 0.3 | 9.01 | ||||||||||||||||||||||||||||||||||
| c.2788C>A | P930T 2D AIThe SynGAP1 missense variant P930T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability analysis is available. Overall, the consensus of the majority of tools supports a pathogenic classification, and this is consistent with the absence of any ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -9.558 | Likely Pathogenic | 0.984 | Likely Pathogenic | Likely Pathogenic | 0.454 | Likely Benign | -5.97 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.67 | Pathogenic | 0.00 | Affected | 0.1666 | 0.5593 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.2788C>G | P930A 2D AIThe SynGAP1 missense variant P930A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P930A is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -8.938 | Likely Pathogenic | 0.963 | Likely Pathogenic | Likely Pathogenic | 0.392 | Likely Benign | -6.03 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 0.68 | Pathogenic | 0.00 | Affected | 0.3376 | 0.4983 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.2788C>T | P930S 2D AIThe SynGAP1 missense variant P930S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P930S is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -8.439 | Likely Pathogenic | 0.984 | Likely Pathogenic | Likely Pathogenic | 0.379 | Likely Benign | -5.84 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.68 | Pathogenic | 0.00 | Affected | 0.3301 | 0.5457 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.2789C>A | P930H 2D AIThe SynGAP1 missense variant P930H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors and high‑accuracy tools indicates that P930H is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -9.824 | Likely Pathogenic | 0.983 | Likely Pathogenic | Likely Pathogenic | 0.497 | Likely Benign | -6.44 | Deleterious | 1.000 | Probably Damaging | 1.000 | Probably Damaging | 0.65 | Pathogenic | 0.00 | Affected | 0.1942 | 0.4392 | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||||||
| c.2789C>G | P930R 2D AIThe SynGAP1 missense variant P930R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the consensus of available predictions indicates that P930R is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry (i.e., no contradictory status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -9.474 | Likely Pathogenic | 0.979 | Likely Pathogenic | Likely Pathogenic | 0.505 | Likely Pathogenic | -6.67 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.66 | Pathogenic | 0.00 | Affected | 0.1460 | 0.3515 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.2789C>T | P930L 2D AIThe SynGAP1 missense variant P930L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 unavailable. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P930L, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.538167 | Disordered | 0.988036 | Binding | 0.304 | 0.855 | 0.375 | -10.690 | Likely Pathogenic | 0.988 | Likely Pathogenic | Likely Pathogenic | 0.440 | Likely Benign | -7.25 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 0.66 | Pathogenic | 0.00 | Affected | 0.2275 | 0.6113 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| c.3229A>C | T1077P 2D AIThe SynGAP1 missense variant T1077P is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence shows AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely benign outcome, and Foldetta results are unavailable. Overall, the majority of predictions and the high‑accuracy consensus point to a benign impact. This conclusion is not contradicted by ClinVar status, which has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | -2.436 | Likely Benign | 0.345 | Ambiguous | Likely Benign | 0.164 | Likely Benign | -0.91 | Neutral | 0.970 | Probably Damaging | 0.787 | Possibly Damaging | 4.16 | Benign | 0.04 | Affected | 0.1876 | 0.4788 | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3229A>G | T1077A 2D AIThe SynGAP1 missense variant T1077A is catalogued in gnomAD (ID 6‑33443781‑A‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports 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 | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | 6-33443781-A-G | -3.303 | Likely Benign | 0.280 | Likely Benign | Likely Benign | 0.153 | Likely Benign | -0.60 | Neutral | 0.288 | Benign | 0.194 | Benign | 4.25 | Benign | 0.10 | Tolerated | 3.77 | 5 | 0.3373 | 0.4393 | 0 | 1 | 2.5 | -30.03 | ||||||||||||||||||||||||||||||||||||
| c.3229A>T | T1077S 2D AIThe SynGAP1 missense variant T1077S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | -2.929 | Likely Benign | 0.201 | Likely Benign | Likely Benign | 0.114 | Likely Benign | -0.45 | Neutral | 0.068 | Benign | 0.025 | Benign | 4.32 | Benign | 0.06 | Tolerated | 0.2788 | 0.4635 | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3230C>A | T1077K 2D  AIThe SynGAP1 missense variant T1077K is not reported 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 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 not available. Overall, the majority of evidence—including the SGM‑Consensus—suggests a benign impact, and this conclusion does not contradict the absence of a ClinVar entry. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | -4.196 | Likely Benign | 0.928 | Likely Pathogenic | Ambiguous | 0.110 | Likely Benign | -1.44 | Neutral | 0.818 | Possibly Damaging | 0.460 | Possibly Damaging | 4.21 | Benign | 0.03 | Affected | 0.1176 | 0.3968 | 0 | -1 | -3.2 | 27.07 | |||||||||||||||||||||||||||||||||||||||
| c.3230C>G | T1077R 2D  AIThe SynGAP1 missense variant T1077R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), which collectively classify the variant as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and no Foldetta stability assessment is available. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | -4.109 | Likely Benign | 0.890 | Likely Pathogenic | Ambiguous | 0.121 | Likely Benign | -1.01 | Neutral | 0.970 | Probably Damaging | 0.728 | Possibly Damaging | 4.18 | Benign | 0.03 | Affected | 0.1028 | 0.3491 | -1 | -1 | -3.8 | 55.08 | |||||||||||||||||||||||||||||||||||||||
| c.3230C>T | T1077I 2D AIThe SynGAP1 missense variant T1077I is listed in gnomAD (ID 6‑33443782‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions (REVEL, PROVEAN, SIFT, ESM1b, FATHMM) and pathogenic predictions (PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, AlphaMissense‑Default). The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, while Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this residue. Taken together, the majority of evidence points toward a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, and there is no contradiction with existing database annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.988141 | Binding | 0.329 | 0.892 | 0.750 | 6-33443782-C-T | 1 | 6.25e-7 | -4.710 | Likely Benign | 0.919 | Likely Pathogenic | Ambiguous | 0.155 | Likely Benign | -1.11 | Neutral | 0.970 | Probably Damaging | 0.787 | Possibly Damaging | 4.19 | Benign | 0.33 | Tolerated | 3.77 | 5 | 0.1135 | 0.5870 | -1 | 0 | 5.2 | 12.05 | ||||||||||||||||||||||||||||||||||
| c.3223C>A | Q1075K 2D AIThe SynGAP1 missense variant Q1075K (ClinVar ID 2762879.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. 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, is “Likely Benign” because three of the four contributing tools predict benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) 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 “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | Uncertain | 1 | -5.135 | Likely Benign | 0.728 | Likely Pathogenic | Likely Benign | 0.134 | Likely Benign | -0.67 | Neutral | 0.963 | Probably Damaging | 0.959 | Probably Damaging | 2.75 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0.1898 | 0.4411 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.3223C>G | Q1075E 2D AIThe SynGAP1 missense variant Q1075E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default remains uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy assessments therefore indicate a benign outcome: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is Likely Benign, and Foldetta data is missing. 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 | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -2.275 | Likely Benign | 0.401 | Ambiguous | Likely Benign | 0.065 | Likely Benign | -0.70 | Neutral | 0.963 | Probably Damaging | 0.959 | Probably Damaging | 2.75 | Benign | 0.25 | Tolerated | 0.1459 | 0.2463 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3224A>C | Q1075P 2D AIThe SynGAP1 missense variant Q1075P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of evidence points to a benign effect, 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 | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -1.854 | Likely Benign | 0.086 | Likely Benign | Likely Benign | 0.175 | Likely Benign | 0.78 | Neutral | 0.996 | Probably Damaging | 0.988 | Probably Damaging | 2.68 | Benign | 0.28 | Tolerated | 0.2288 | 0.5741 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3224A>G | Q1075R 2D AIThe SynGAP1 missense variant Q1075R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise 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 effect, and this conclusion does not contradict any ClinVar status, as none is assigned to the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -5.039 | Likely Benign | 0.697 | Likely Pathogenic | Likely Benign | 0.142 | Likely Benign | -0.37 | Neutral | 0.985 | Probably Damaging | 0.973 | Probably Damaging | 2.72 | Benign | 0.93 | Tolerated | 0.1504 | 0.2650 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3224A>T | Q1075L 2D AIThe SynGAP1 missense variant Q1075L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for Q1075L, and this conclusion is consistent with the absence of a ClinVar assertion. The variant is most likely benign based on predictions, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -3.976 | Likely Benign | 0.209 | Likely Benign | Likely Benign | 0.128 | Likely Benign | -2.10 | Neutral | 0.985 | Probably Damaging | 0.973 | Probably Damaging | 2.72 | Benign | 0.15 | Tolerated | 0.0888 | 0.6454 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3225G>C | Q1075H 2D AIThe SynGAP1 missense variant Q1075H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM‑Consensus also indicates likely benign, while Foldetta data is missing. Overall, the majority of reliable predictors classify the variant as 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 | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -4.616 | Likely Benign | 0.486 | Ambiguous | Likely Benign | 0.072 | Likely Benign | -1.06 | Neutral | 0.996 | Probably Damaging | 0.992 | Probably Damaging | 2.68 | Benign | 0.13 | Tolerated | 0.1457 | 0.4214 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3225G>T | Q1075H 2D AIThe SynGAP1 missense variant Q1075H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM‑Consensus also indicates likely benign, while Foldetta data is missing. Overall, the majority of reliable predictors classify the variant as 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 | 0.922952 | Disordered | 0.988305 | Binding | 0.354 | 0.894 | 0.750 | -4.616 | Likely Benign | 0.486 | Ambiguous | Likely Benign | 0.072 | Likely Benign | -1.06 | Neutral | 0.996 | Probably Damaging | 0.992 | Probably Damaging | 2.68 | Benign | 0.13 | Tolerated | 0.1457 | 0.4214 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.2794T>A | F932I 2D AIThe SynGAP1 missense variant F932I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic because three of the four constituent tools predict pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is also pathogenic; Foldetta results are unavailable. Consequently, the collective evidence points to a pathogenic effect for F932I. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -4.963 | Likely Benign | 0.982 | Likely Pathogenic | Likely Pathogenic | 0.348 | Likely Benign | -3.45 | Deleterious | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.32 | Pathogenic | 0.01 | Affected | 0.2202 | 0.2914 | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2794T>C | F932L 2D AIThe SynGAP1 missense variant F932L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (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) also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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 | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -3.390 | Likely Benign | 0.995 | Likely Pathogenic | Likely Pathogenic | 0.309 | Likely Benign | -3.50 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.36 | Pathogenic | 0.03 | Affected | 0.2373 | 0.3895 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2794T>G | F932V 2D AIThe SynGAP1 missense variant F932V 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -5.728 | Likely Benign | 0.976 | Likely Pathogenic | Likely Pathogenic | 0.392 | Likely Benign | -3.68 | Deleterious | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.32 | Pathogenic | 0.01 | Affected | 0.2137 | 0.3082 | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||||||
| c.2795T>A | F932Y 2D AIThe SynGAP1 missense variant F932Y is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. When predictions are grouped by agreement, the benign‑predicating tools outnumber the pathogenic ones, and the single uncertain call from AlphaMissense‑Default does not alter this balance. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. Foldetta data are unavailable. Overall, the computational evidence overwhelmingly supports a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -5.248 | Likely Benign | 0.540 | Ambiguous | Likely Benign | 0.180 | Likely Benign | 1.58 | Neutral | 0.997 | Probably Damaging | 0.987 | Probably Damaging | 3.13 | Benign | 0.74 | Tolerated | 0.1473 | 0.2003 | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||||||
| c.2795T>C | F932S 2D AIThe SynGAP1 missense variant F932S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that F932S 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 | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -7.196 | In-Between | 0.993 | Likely Pathogenic | Likely Pathogenic | 0.260 | Likely Benign | -4.45 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.31 | Pathogenic | 0.00 | Affected | 0.4257 | 0.0584 | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||||||
| c.2795T>G | F932C 2D AIThe SynGAP1 missense variant F932C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 unavailable. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools indicates that the F932C variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -8.601 | Likely Pathogenic | 0.982 | Likely Pathogenic | Likely Pathogenic | 0.309 | Likely Benign | -4.62 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.30 | Pathogenic | 0.00 | Affected | 0.2446 | 0.1506 | -4 | -2 | -0.3 | -44.04 | |||||||||||||||||||||||||||||||||||||||
| c.2796C>A | F932L 2D AIThe SynGAP1 missense variant F932L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (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) also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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 | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -3.390 | Likely Benign | 0.995 | Likely Pathogenic | Likely Pathogenic | 0.170 | Likely Benign | -3.50 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.36 | Pathogenic | 0.03 | Affected | 0.2373 | 0.3895 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2796C>G | F932L 2D AIThe SynGAP1 missense variant F932L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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 | 0.675549 | Disordered | 0.989197 | Binding | 0.293 | 0.858 | 0.500 | -3.390 | Likely Benign | 0.995 | Likely Pathogenic | Likely Pathogenic | 0.170 | Likely Benign | -3.50 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.36 | Pathogenic | 0.03 | Affected | 0.2373 | 0.3895 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||||||
| c.2791C>A | L931I 2D AIThe SynGAP1 missense variant L931I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 HumDiv and polyPhen‑2 HumVar both predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -3.813 | Likely Benign | 0.296 | Likely Benign | Likely Benign | 0.120 | Likely Benign | 0.42 | Neutral | 0.999 | Probably Damaging | 0.994 | Probably Damaging | 2.58 | Benign | 0.14 | Tolerated | 0.1076 | 0.3540 | 2 | 2 | 0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.2791C>G | L931V 2D AIThe SynGAP1 missense variant L931V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for the L931V variant, and this conclusion does not contradict any ClinVar annotation, as none exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -1.512 | Likely Benign | 0.234 | Likely Benign | Likely Benign | 0.182 | Likely Benign | 0.71 | Neutral | 0.999 | Probably Damaging | 0.994 | Probably Damaging | 3.03 | Benign | 0.70 | Tolerated | 0.1690 | 0.3164 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.2791C>T | L931F 2D AIThe SynGAP1 missense variant L931F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a 2‑to‑2 split, leaving the consensus inconclusive. Foldetta, which assesses protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Consequently, the overall evidence leans toward pathogenicity, driven by the majority of standard predictors, and does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -5.101 | Likely Benign | 0.790 | Likely Pathogenic | Ambiguous | 0.167 | Likely Benign | -2.00 | Neutral | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.41 | Pathogenic | 0.04 | Affected | 0.0718 | 0.3208 | 2 | 0 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||||||||
| c.2792T>A | L931H 2D AIThe SynGAP1 missense variant L931H has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. ESM1b and AlphaMissense‑Optimized are uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, 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 | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -7.495 | In-Between | 0.954 | Likely Pathogenic | Ambiguous | 0.301 | Likely Benign | -3.76 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.38 | Pathogenic | 0.00 | Affected | 0.1198 | 0.1205 | -2 | -3 | -7.0 | 23.98 | |||||||||||||||||||||||||||||||||||||||
| c.2792T>C | L931P 2D AIThe SynGAP1 missense variant L931P is not reported in ClinVar and is absent from gnomAD. Prediction tools show a strong bias toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default all predict a deleterious effect, whereas only REVEL indicates a benign outcome. High‑accuracy assessments reinforce this trend: the SGM consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic, and AlphaMissense‑Optimized returns an uncertain result. Foldetta predictions are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for L931P, and this conclusion is consistent with the absence of any 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 Pathogenic | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -8.624 | Likely Pathogenic | 0.950 | Likely Pathogenic | Ambiguous | 0.376 | Likely Benign | -3.43 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.38 | Pathogenic | 0.01 | Affected | 0.3203 | 0.1698 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||||||
| c.2792T>G | L931R 2D AIThe SynGAP1 missense variant L931R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.549308 | Disordered | 0.989212 | Binding | 0.335 | 0.856 | 0.375 | -8.606 | Likely Pathogenic | 0.933 | Likely Pathogenic | Ambiguous | 0.344 | Likely Benign | -3.48 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.39 | Pathogenic | 0.01 | Affected | 0.1241 | 0.1205 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.3103C>A | P1035T 2D AIThe SynGAP1 missense variant P1035T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence from AlphaMissense‑Optimized and the SGM‑Consensus both support a benign classification, while the absence of a Foldetta result does not alter this view. Overall, the majority of predictions indicate a benign effect, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | Uncertain | 1 | -4.447 | Likely Benign | 0.426 | Ambiguous | Likely Benign | 0.087 | Likely Benign | -0.96 | Neutral | 0.901 | Possibly Damaging | 0.537 | Possibly Damaging | 2.72 | Benign | 0.23 | Tolerated | 3.77 | 5 | 0.1628 | 0.7220 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||
| c.3103C>G | P1035A 2D AIThe SynGAP1 missense variant P1035A 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 points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | -4.293 | Likely Benign | 0.241 | Likely Benign | Likely Benign | 0.041 | Likely Benign | -1.02 | Neutral | 0.481 | Possibly Damaging | 0.222 | Benign | 2.74 | Benign | 0.41 | Tolerated | 0.3188 | 0.6022 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||||||
| c.3103C>T | P1035S 2D AIThe SynGAP1 missense variant P1035S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact for P1035S, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | -3.678 | Likely Benign | 0.341 | Ambiguous | Likely Benign | 0.059 | Likely Benign | -0.97 | Neutral | 0.818 | Possibly Damaging | 0.355 | Benign | 2.79 | Benign | 0.28 | Tolerated | 0.3257 | 0.6253 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3104C>A | P1035H 2D AIThe SynGAP1 missense variant P1035H is not reported in ClinVar and has no entries in gnomAD. Consensus predictions from multiple in‑silico tools are mixed: benign calls come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | -5.333 | Likely Benign | 0.608 | Likely Pathogenic | Likely Benign | 0.058 | Likely Benign | -0.76 | Neutral | 0.997 | Probably Damaging | 0.889 | Possibly Damaging | 2.68 | Benign | 0.15 | Tolerated | 0.1893 | 0.5669 | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||||||
| c.3104C>G | P1035R 2D AIThe SynGAP1 missense variant P1035R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, 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 the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | -4.534 | Likely Benign | 0.604 | Likely Pathogenic | Likely Benign | 0.119 | Likely Benign | 1.07 | Neutral | 0.970 | Probably Damaging | 0.728 | Possibly Damaging | 2.89 | Benign | 0.93 | Tolerated | 0.1424 | 0.4201 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3104C>T | P1035L 2D AIThe SynGAP1 missense variant P1035L is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, 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 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 for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.945666 | Disordered | 0.989572 | Binding | 0.300 | 0.756 | 0.625 | -5.694 | Likely Benign | 0.675 | Likely Pathogenic | Likely Benign | 0.071 | Likely Benign | -2.11 | Neutral | 0.970 | Probably Damaging | 0.728 | Possibly Damaging | 2.70 | Benign | 0.21 | Tolerated | 0.2444 | 0.7354 | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||||||
| c.3226T>A | L1076M 2D AIThe SynGAP1 missense variant L1076M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -5.047 | Likely Benign | 0.320 | Likely Benign | Likely Benign | 0.087 | Likely Benign | 0.02 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 2.42 | Pathogenic | 0.04 | Affected | 0.0886 | 0.4147 | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3226T>G | L1076V 2D AIThe SynGAP1 missense variant L1076V is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -3.615 | Likely Benign | 0.344 | Ambiguous | Likely Benign | 0.097 | Likely Benign | -0.56 | Neutral | 0.995 | Probably Damaging | 0.982 | Probably Damaging | 2.53 | Benign | 0.11 | Tolerated | 0.1632 | 0.3781 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3227T>C | L1076S 2D AIThe SynGAP1 missense variant L1076S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes); and Foldetta results are unavailable. Consequently, the evidence is evenly split between benign and pathogenic predictions. The variant is therefore most likely of uncertain significance, 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. | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -2.975 | Likely Benign | 0.913 | Likely Pathogenic | Ambiguous | 0.225 | Likely Benign | 0.55 | Neutral | 0.999 | Probably Damaging | 0.983 | Probably Damaging | 2.43 | Pathogenic | 0.75 | Tolerated | 0.3045 | 0.1178 | -3 | -2 | -4.6 | -26.08 | ||||||||||||||||||||||||||||||||||||||||
| c.3227T>G | L1076W 2D AIThe SynGAP1 missense variant L1076W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) lean toward a pathogenic interpretation. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -6.377 | Likely Benign | 0.822 | Likely Pathogenic | Ambiguous | 0.183 | Likely Benign | -1.40 | Neutral | 1.000 | Probably Damaging | 0.996 | Probably Damaging | 2.38 | Pathogenic | 0.02 | Affected | 0.0749 | 0.3740 | -2 | -2 | -4.7 | 73.05 | ||||||||||||||||||||||||||||||||||||||||
| c.3228G>C | L1076F 2D AIThe SynGAP1 missense variant L1076F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -4.606 | Likely Benign | 0.675 | Likely Pathogenic | Likely Benign | 0.092 | Likely Benign | -0.92 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 2.42 | Pathogenic | 0.03 | Affected | 0.0759 | 0.3767 | 2 | 0 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||||||||
| c.3228G>T | L1076F 2D AIThe SynGAP1 missense variant L1076F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.922952 | Disordered | 0.989617 | Binding | 0.301 | 0.892 | 0.750 | -4.606 | Likely Benign | 0.675 | Likely Pathogenic | Likely Benign | 0.092 | Likely Benign | -0.92 | Neutral | 0.999 | Probably Damaging | 0.995 | Probably Damaging | 2.42 | Pathogenic | 0.03 | Affected | 0.0759 | 0.3767 | 2 | 0 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||||||||
| c.3067T>A | S1023T 2D AIThe SynGAP1 missense variant S1023T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.831250 | Disordered | 0.990262 | Binding | 0.322 | 0.750 | 0.500 | -5.573 | Likely Benign | 0.360 | Ambiguous | Likely Benign | 0.092 | Likely Benign | -1.62 | Neutral | 0.979 | Probably Damaging | 0.982 | Probably Damaging | 2.49 | Pathogenic | 0.04 | Affected | 0.1299 | 0.5370 | 1 | 1 | 0.1 | 14.03 | ||||||||||||||||||||||||||||||||||||||||
| c.3067T>C | S1023P 2D AIThe SynGAP1 missense variant S1023P is reported in gnomAD (ID 6‑33443619‑T‑C) but has no ClinVar entry (ClinVar status: not reported). Functional prediction tools are split: benign calls come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM Consensus remains inconclusive, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of standard predictors lean toward pathogenicity, whereas the few high‑accuracy tools do not support a pathogenic verdict. Thus, the variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.831250 | Disordered | 0.990262 | Binding | 0.322 | 0.750 | 0.500 | 6-33443619-T-C | 2 | 1.24e-6 | -5.634 | Likely Benign | 0.679 | Likely Pathogenic | Likely Benign | 0.146 | Likely Benign | -2.11 | Neutral | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.43 | Pathogenic | 0.02 | Affected | 3.77 | 5 | 0.1818 | 0.4616 | -1 | 1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||
| c.3067T>G | S1023A 2D AIThe SynGAP1 missense variant S1023A is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of pathogenic predictors—polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT—suggest a damaging impact. The AlphaMissense‑Default score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools therefore lean toward a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and no Foldetta data is available. Overall, the computational evidence supports a benign classification, 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 | 0.831250 | Disordered | 0.990262 | Binding | 0.322 | 0.750 | 0.500 | -6.031 | Likely Benign | 0.356 | Ambiguous | Likely Benign | 0.098 | Likely Benign | -1.59 | Neutral | 0.979 | Probably Damaging | 0.982 | Probably Damaging | 2.53 | Benign | 0.04 | Affected | 0.4427 | 0.4386 | 1 | 1 | 2.6 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3068C>T | S1023L 2D  AIThe SynGAP1 missense variant S1023L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of tools and the SGM‑Consensus indicates a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.831250 | Disordered | 0.990262 | Binding | 0.322 | 0.750 | 0.500 | -5.735 | Likely Benign | 0.705 | Likely Pathogenic | Likely Benign | 0.204 | Likely Benign | -3.47 | Deleterious | 0.991 | Probably Damaging | 0.991 | Probably Damaging | 2.47 | Pathogenic | 0.01 | Affected | 0.1080 | 0.4923 | -3 | -2 | 4.6 | 26.08 | |||||||||||||||||||||||||||||||||||||||
| c.3100C>A | P1034T 2D AIThe SynGAP1 missense variant P1034T is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools predict a pathogenic outcome: SIFT and FATHMM. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | -4.367 | Likely Benign | 0.285 | Likely Benign | Likely Benign | 0.026 | Likely Benign | -2.00 | Neutral | 0.126 | Benign | 0.096 | Benign | 2.44 | Pathogenic | 0.03 | Affected | 0.1518 | 0.6620 | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||||||
| c.3100C>G | P1034A 2D AIThe SynGAP1 missense variant P1034A is listed in ClinVar as Benign (ClinVar ID 1901716.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome, representing the sole discordant signal. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates a benign impact. This prediction aligns with the ClinVar status, with no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | Benign | 1 | -4.174 | Likely Benign | 0.178 | Likely Benign | Likely Benign | 0.060 | Likely Benign | -2.44 | Neutral | 0.059 | Benign | 0.061 | Benign | 2.47 | Pathogenic | 0.06 | Tolerated | 3.77 | 5 | 0.3028 | 0.5622 | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.3100C>T | P1034S 2D AIThe SynGAP1 missense variant P1034S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for P1034S, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | -3.730 | Likely Benign | 0.262 | Likely Benign | Likely Benign | 0.054 | Likely Benign | -2.28 | Neutral | 0.011 | Benign | 0.015 | Benign | 2.44 | Pathogenic | 0.05 | Affected | 0.3044 | 0.5853 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3101C>A | P1034H 2D AIThe SynGAP1 missense variant P1034H is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | -4.634 | Likely Benign | 0.540 | Ambiguous | Likely Benign | 0.083 | Likely Benign | -3.17 | Deleterious | 0.938 | Possibly Damaging | 0.750 | Possibly Damaging | 2.38 | Pathogenic | 0.02 | Affected | 0.1776 | 0.5451 | 0 | -2 | -1.6 | 40.02 | ||||||||||||||||||||||||||||||||||||||||
| c.3101C>G | P1034R 2D AIThe SynGAP1 P1034R variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the predictions are mixed, with a slight tilt toward pathogenicity due to the SGM Consensus result and the number of pathogenic calls. The variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | -3.666 | Likely Benign | 0.676 | Likely Pathogenic | Likely Benign | 0.073 | Likely Benign | -3.04 | Deleterious | 0.002 | Benign | 0.005 | Benign | 2.40 | Pathogenic | 0.02 | Affected | 0.1366 | 0.4182 | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||||||
| c.3101C>T | P1034L 2D AIThe SynGAP1 missense variant P1034L is not 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 and SIFT, while AlphaMissense‑Default is uncertain. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign prediction (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 consensus of available predictions indicates that P1034L is most likely benign, 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. | 0.926919 | Disordered | 0.991713 | Binding | 0.343 | 0.752 | 0.625 | -4.204 | Likely Benign | 0.449 | Ambiguous | Likely Benign | 0.067 | Likely Benign | -3.24 | Deleterious | 0.001 | Benign | 0.005 | Benign | 2.53 | Benign | 0.01 | Affected | 0.2267 | 0.6937 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3070C>A | L1024I 2D AIThe SynGAP1 missense variant L1024I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -4.794 | Likely Benign | 0.260 | Likely Benign | Likely Benign | 0.062 | Likely Benign | -0.99 | Neutral | 0.959 | Probably Damaging | 0.642 | Possibly Damaging | 2.45 | Pathogenic | 0.11 | Tolerated | 0.0992 | 0.3735 | 2 | 2 | 0.7 | 0.00 | |||||||||||||||||||||||||||||||||||||||
| c.3070C>G | L1024V 2D AIThe SynGAP1 missense variant L1024V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -3.758 | Likely Benign | 0.244 | Likely Benign | Likely Benign | 0.041 | Likely Benign | -1.33 | Neutral | 0.907 | Possibly Damaging | 0.642 | Possibly Damaging | 2.47 | Pathogenic | 0.08 | Tolerated | 0.1459 | 0.3185 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3070C>T | L1024F 2D AIThe SynGAP1 missense variant L1024F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains both benign and pathogenic calls. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -5.133 | Likely Benign | 0.544 | Ambiguous | Likely Benign | 0.059 | Likely Benign | -2.08 | Neutral | 0.994 | Probably Damaging | 0.924 | Probably Damaging | 2.40 | Pathogenic | 0.07 | Tolerated | 0.0706 | 0.3708 | 2 | 0 | -1.0 | 34.02 | ||||||||||||||||||||||||||||||||||||||||
| c.3071T>A | L1024H 2D AIThe SynGAP1 missense variant L1024H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta data are unavailable. Overall, the majority of evidence points toward a deleterious effect, suggesting the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -3.271 | Likely Benign | 0.868 | Likely Pathogenic | Ambiguous | 0.123 | Likely Benign | -3.09 | Deleterious | 1.000 | Probably Damaging | 0.981 | Probably Damaging | 2.38 | Pathogenic | 0.01 | Affected | 0.1198 | 0.1483 | -2 | -3 | -7.0 | 23.98 | |||||||||||||||||||||||||||||||||||||||
| c.3071T>C | L1024P 2D AIThe SynGAP1 missense variant L1024P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard prediction tools lean toward pathogenicity, while high‑accuracy methods are inconclusive. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -4.385 | Likely Benign | 0.730 | Likely Pathogenic | Likely Benign | 0.149 | Likely Benign | -2.42 | Neutral | 0.999 | Probably Damaging | 0.974 | Probably Damaging | 2.43 | Pathogenic | 0.03 | Affected | 0.3187 | 0.2033 | -3 | -3 | -5.4 | -16.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3071T>G | L1024R 2D AIThe SynGAP1 missense variant L1024R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic interpretation. This assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.862302 | Disordered | 0.992699 | Binding | 0.327 | 0.753 | 0.500 | -3.434 | Likely Benign | 0.841 | Likely Pathogenic | Ambiguous | 0.148 | Likely Benign | -2.41 | Neutral | 0.997 | Probably Damaging | 0.962 | Probably Damaging | 2.40 | Pathogenic | 0.02 | Affected | 0.1335 | 0.1557 | -3 | -2 | -8.3 | 43.03 | ||||||||||||||||||||||||||||||||||||||||
| c.3073C>A | Q1025K 2D AIThe SynGAP1 missense variant Q1025K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas the only pathogenic call is from polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which has no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -4.510 | Likely Benign | 0.529 | Ambiguous | Likely Benign | 0.041 | Likely Benign | -1.09 | Neutral | 0.649 | Possibly Damaging | 0.353 | Benign | 2.78 | Benign | 0.22 | Tolerated | 0.1690 | 0.4438 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3073C>G | Q1025E 2D AIThe SynGAP1 missense variant Q1025E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise 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 consensus of available predictions 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 | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -3.010 | Likely Benign | 0.254 | Likely Benign | Likely Benign | 0.077 | Likely Benign | -0.60 | Neutral | 0.649 | Possibly Damaging | 0.353 | Benign | 2.79 | Benign | 1.00 | Tolerated | 0.1391 | 0.2269 | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3074A>C | Q1025P 2D AIThe SynGAP1 missense variant Q1025P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this conclusion 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 | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -2.151 | Likely Benign | 0.211 | Likely Benign | Likely Benign | 0.153 | Likely Benign | -1.22 | Neutral | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.72 | Benign | 0.11 | Tolerated | 0.2211 | 0.5196 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3074A>G | Q1025R 2D AIThe SynGAP1 missense variant Q1025R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -4.435 | Likely Benign | 0.480 | Ambiguous | Likely Benign | 0.101 | Likely Benign | -1.28 | Neutral | 0.818 | Possibly Damaging | 0.453 | Possibly Damaging | 2.72 | Benign | 0.10 | Tolerated | 0.1342 | 0.2656 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3074A>T | Q1025L 2D AIThe SynGAP1 missense variant Q1025L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -6.460 | Likely Benign | 0.463 | Ambiguous | Likely Benign | 0.117 | Likely Benign | -2.48 | Neutral | 0.901 | Possibly Damaging | 0.534 | Possibly Damaging | 2.70 | Benign | 0.05 | Affected | 0.0798 | 0.5497 | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3075G>C | Q1025H 2D AIThe SynGAP1 missense variant Q1025H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. 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 classify the variant as benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -4.976 | Likely Benign | 0.405 | Ambiguous | Likely Benign | 0.051 | Likely Benign | -1.43 | Neutral | 0.014 | Benign | 0.012 | Benign | 2.68 | Benign | 0.05 | Affected | 0.1332 | 0.3852 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3075G>T | Q1025H 2D AIThe SynGAP1 missense variant Q1025H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. 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 classify the variant as benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.879233 | Disordered | 0.993410 | Binding | 0.363 | 0.746 | 0.500 | -4.976 | Likely Benign | 0.405 | Ambiguous | Likely Benign | 0.051 | Likely Benign | -1.43 | Neutral | 0.014 | Benign | 0.012 | Benign | 2.68 | Benign | 0.05 | Affected | 0.1332 | 0.3852 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3097T>A | S1033T 2D AIThe SynGAP1 missense variant S1033T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the 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 | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | -3.702 | Likely Benign | 0.140 | Likely Benign | Likely Benign | 0.029 | Likely Benign | -0.05 | Neutral | 0.568 | Possibly Damaging | 0.171 | Benign | 2.73 | Benign | 0.58 | Tolerated | 0.1379 | 0.6089 | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3097T>C | S1033P 2D AIThe SynGAP1 missense variant S1033P is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. 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: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are not available, so they do not influence the overall assessment. Based on the consensus of all available predictions, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | -2.046 | Likely Benign | 0.268 | Likely Benign | Likely Benign | 0.068 | Likely Benign | 0.05 | Neutral | 0.002 | Benign | 0.005 | Benign | 2.68 | Benign | 0.27 | Tolerated | 0.1889 | 0.5486 | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||||||
| c.3097T>G | S1033A 2D AIThe SynGAP1 missense variant S1033A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions indicates that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | -3.107 | Likely Benign | 0.121 | Likely Benign | Likely Benign | 0.033 | Likely Benign | 0.06 | Neutral | 0.220 | Benign | 0.085 | Benign | 2.81 | Benign | 1.00 | Tolerated | 0.4387 | 0.5282 | 1 | 1 | 2.6 | -16.00 | |||||||||||||||||||||||||||||||||||||||
| c.3098C>A | S1033Y 2D AIThe SynGAP1 missense variant S1033Y is reported in gnomAD (ID 6‑33443650‑C‑A) but has no ClinVar entry. 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 is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | 6-33443650-C-A | 1 | 6.19e-7 | -4.857 | Likely Benign | 0.564 | Ambiguous | Likely Benign | 0.034 | Likely Benign | -1.01 | Neutral | 0.021 | Benign | 0.008 | Benign | 2.69 | Benign | 0.04 | Affected | 3.77 | 5 | 0.0708 | 0.5262 | -2 | -3 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||||
| c.3098C>G | S1033C 2D AIThe SynGAP1 missense variant S1033C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S1033C, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | -6.263 | Likely Benign | 0.198 | Likely Benign | Likely Benign | 0.044 | Likely Benign | -0.39 | Neutral | 0.992 | Probably Damaging | 0.750 | Possibly Damaging | 2.68 | Benign | 0.12 | Tolerated | 0.1031 | 0.5704 | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||||||
| c.3098C>T | S1033F 2D AIThe SynGAP1 missense variant S1033F 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 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 is 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 is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.910643 | Disordered | 0.993473 | Binding | 0.294 | 0.737 | 0.625 | -5.013 | Likely Benign | 0.555 | Ambiguous | Likely Benign | 0.022 | Likely Benign | -1.02 | Neutral | 0.440 | Benign | 0.185 | Benign | 2.70 | Benign | 0.05 | Affected | 0.0699 | 0.5546 | -3 | -2 | 3.6 | 60.10 | |||||||||||||||||||||||||||||||||||||||
| c.3076G>A | D1026N 2D AIThe SynGAP1 D1026N variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, 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 and therefore reports a likely benign outcome. AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -4.166 | Likely Benign | 0.608 | Likely Pathogenic | Likely Benign | 0.117 | Likely Benign | -2.07 | Neutral | 0.411 | Benign | 0.239 | Benign | 2.55 | Benign | 0.01 | Affected | 0.1240 | 0.5060 | 2 | 1 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3076G>C | D1026H 2D AIThe SynGAP1 missense variant D1026H is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443628‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. 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. | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | 6-33443628-G-C | 1 | 6.20e-7 | -4.412 | Likely Benign | 0.900 | Likely Pathogenic | Ambiguous | 0.105 | Likely Benign | -2.03 | Neutral | 0.832 | Possibly Damaging | 0.600 | Possibly Damaging | 2.48 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0.1470 | 0.5345 | -1 | 1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||
| c.3076G>T | D1026Y 2D AIThe SynGAP1 missense variant D1026Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -6.999 | Likely Benign | 0.892 | Likely Pathogenic | Ambiguous | 0.200 | Likely Benign | -3.08 | Deleterious | 0.938 | Possibly Damaging | 0.596 | Possibly Damaging | 2.47 | Pathogenic | 0.00 | Affected | 0.0676 | 0.4936 | -4 | -3 | 2.2 | 48.09 | |||||||||||||||||||||||||||||||||||||||
| c.3077A>C | D1026A 2D AIThe SynGAP1 D1026A variant is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. 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 are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a tie, and Foldetta results are not available. Overall, the majority of standard tools favor a benign interpretation, and no ClinVar entry contradicts this assessment. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -4.211 | Likely Benign | 0.849 | Likely Pathogenic | Ambiguous | 0.070 | Likely Benign | -2.69 | Deleterious | 0.112 | Benign | 0.061 | Benign | 2.53 | Benign | 0.02 | Affected | 0.3392 | 0.5279 | 0 | -2 | 5.3 | -44.01 | ||||||||||||||||||||||||||||||||||||||||
| c.3077A>G | D1026G 2D AIThe SynGAP1 missense variant D1026G is not 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of 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. | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -4.125 | Likely Benign | 0.691 | Likely Pathogenic | Likely Benign | 0.098 | Likely Benign | -2.84 | Deleterious | 0.001 | Benign | 0.005 | Benign | 2.67 | Benign | 0.01 | Affected | 0.3377 | 0.5042 | 1 | -1 | 3.1 | -58.04 | ||||||||||||||||||||||||||||||||||||||||
| c.3077A>T | D1026V 2D AIThe SynGAP1 missense variant D1026V is not 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 ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore also indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available, so it does not contribute evidence. Overall, the majority of reliable predictors classify the variant as pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -5.871 | Likely Benign | 0.900 | Likely Pathogenic | Ambiguous | 0.144 | Likely Benign | -3.13 | Deleterious | 0.004 | Benign | 0.004 | Benign | 2.48 | Pathogenic | 0.00 | Affected | 0.0957 | 0.5236 | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||||||
| c.3078C>A | D1026E 2D AIThe SynGAP1 missense variant D1026E is not reported in ClinVar and is absent from gnomAD. All available in silico predictors classify the change as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this 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 | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -3.431 | Likely Benign | 0.190 | Likely Benign | Likely Benign | 0.055 | Likely Benign | -0.37 | Neutral | 0.001 | Benign | 0.005 | Benign | 2.73 | Benign | 0.56 | Tolerated | 0.1449 | 0.4783 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3078C>G | D1026E 2D AIThe SynGAP1 missense variant D1026E is not reported in ClinVar and is absent from gnomAD. All available in silico predictors classify the change as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this 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 | 0.894241 | Disordered | 0.993931 | Binding | 0.324 | 0.739 | 0.500 | -3.431 | Likely Benign | 0.190 | Likely Benign | Likely Benign | 0.055 | Likely Benign | -0.37 | Neutral | 0.001 | Benign | 0.005 | Benign | 2.73 | Benign | 0.56 | Tolerated | 0.1449 | 0.4783 | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3079A>C | N1027H 2D AIThe SynGAP1 missense variant N1027H 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. In contrast, polyPhen‑2 (HumDiv and HumVar) predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy 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 predictions, including the high‑accuracy tools, indicate that 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 | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -4.185 | Likely Benign | 0.193 | Likely Benign | Likely Benign | 0.074 | Likely Benign | -1.44 | Neutral | 0.970 | Probably Damaging | 0.799 | Possibly Damaging | 2.74 | Benign | 0.07 | Tolerated | 0.1345 | 0.7176 | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||||||
| c.3079A>G | N1027D 2D AIThe SynGAP1 missense variant N1027D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, and AlphaMissense‑Default remains uncertain. High‑accuracy tools reinforce the benign assessment: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation, 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 | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -2.891 | Likely Benign | 0.458 | Ambiguous | Likely Benign | 0.073 | Likely Benign | -1.27 | Neutral | 0.649 | Possibly Damaging | 0.353 | Benign | 2.74 | Benign | 0.27 | Tolerated | 0.1854 | 0.4004 | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||||||
| c.3079A>T | N1027Y 2D AIThe SynGAP1 missense variant N1027Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -5.799 | Likely Benign | 0.626 | Likely Pathogenic | Likely Benign | 0.074 | Likely Benign | -2.15 | Neutral | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.70 | Benign | 0.03 | Affected | 0.0611 | 0.6133 | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||||||
| c.3080A>C | N1027T 2D AIThe SynGAP1 missense variant N1027T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the absence of any ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -3.604 | Likely Benign | 0.199 | Likely Benign | Likely Benign | 0.046 | Likely Benign | -0.71 | Neutral | 0.481 | Possibly Damaging | 0.220 | Benign | 2.75 | Benign | 0.13 | Tolerated | 0.1239 | 0.7188 | 0 | 0 | 2.8 | -13.00 | |||||||||||||||||||||||||||||||||||||||
| c.3080A>G | N1027S 2D AIThe SynGAP1 missense variant N1027S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective predictions strongly suggest that the variant is most likely benign, and this conclusion 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 | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -2.443 | Likely Benign | 0.093 | Likely Benign | Likely Benign | 0.088 | Likely Benign | -0.35 | Neutral | 0.068 | Benign | 0.039 | Benign | 2.77 | Benign | 0.50 | Tolerated | 0.3540 | 0.6874 | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||||||
| c.3080A>T | N1027I 2D AIThe SynGAP1 missense variant N1027I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -5.847 | Likely Benign | 0.751 | Likely Pathogenic | Likely Benign | 0.065 | Likely Benign | -2.36 | Neutral | 0.970 | Probably Damaging | 0.726 | Possibly Damaging | 2.71 | Benign | 0.02 | Affected | 0.0677 | 0.5724 | -2 | -3 | 8.0 | -0.94 | |||||||||||||||||||||||||||||||||||||||
| c.3081C>A | N1027K 2D AIThe SynGAP1 missense variant N1027K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv 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 favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -3.177 | Likely Benign | 0.841 | Likely Pathogenic | Ambiguous | 0.063 | Likely Benign | -0.64 | Neutral | 0.481 | Possibly Damaging | 0.220 | Benign | 2.81 | Benign | 0.65 | Tolerated | 0.1808 | 0.6079 | 1 | 0 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||||
| c.3081C>G | N1027K 2D AIThe SynGAP1 missense variant N1027K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. 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 | 0.831250 | Disordered | 0.994357 | Binding | 0.347 | 0.745 | 0.500 | -3.177 | Likely Benign | 0.841 | Likely Pathogenic | Ambiguous | 0.063 | Likely Benign | -0.64 | Neutral | 0.481 | Possibly Damaging | 0.220 | Benign | 2.81 | Benign | 0.65 | Tolerated | 0.1808 | 0.6079 | 1 | 0 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||||||||
| c.3082C>A | L1028M 2D AIThe SynGAP1 missense variant L1028M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.995137 | Binding | 0.364 | 0.730 | 0.500 | -4.591 | Likely Benign | 0.229 | Likely Benign | Likely Benign | 0.082 | Likely Benign | -0.07 | Neutral | 0.986 | Probably Damaging | 0.825 | Possibly Damaging | 2.70 | Benign | 0.18 | Tolerated | 0.0776 | 0.3124 | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3082C>G | L1028V 2D AIThe SynGAP1 missense variant L1028V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of computational evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.995137 | Binding | 0.364 | 0.730 | 0.500 | -3.992 | Likely Benign | 0.217 | Likely Benign | Likely Benign | 0.042 | Likely Benign | -0.68 | Neutral | 0.737 | Possibly Damaging | 0.376 | Benign | 2.74 | Benign | 0.26 | Tolerated | 0.1328 | 0.2715 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3083T>A | L1028Q 2D AIThe SynGAP1 missense variant L1028Q is not reported 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 | 0.899122 | Disordered | 0.995137 | Binding | 0.364 | 0.730 | 0.500 | -2.718 | Likely Benign | 0.612 | Likely Pathogenic | Likely Benign | 0.179 | Likely Benign | -0.19 | Neutral | 0.986 | Probably Damaging | 0.825 | Possibly Damaging | 2.80 | Benign | 0.38 | Tolerated | 0.1110 | 0.1403 | -2 | -2 | -7.3 | 14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3083T>C | L1028P 2D AIThe SynGAP1 missense variant L1028P 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, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for this variant, and 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 | 0.899122 | Disordered | 0.995137 | Binding | 0.364 | 0.730 | 0.500 | -3.080 | Likely Benign | 0.594 | Likely Pathogenic | Likely Benign | 0.215 | Likely Benign | -0.42 | Neutral | 0.004 | Benign | 0.010 | Benign | 2.70 | Benign | 0.25 | Tolerated | 0.2846 | 0.1763 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||||||
| c.3083T>G | L1028R 2D AIThe SynGAP1 missense variant L1028R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.899122 | Disordered | 0.995137 | Binding | 0.364 | 0.730 | 0.500 | -2.204 | Likely Benign | 0.793 | Likely Pathogenic | Ambiguous | 0.167 | Likely Benign | -0.24 | Neutral | 0.960 | Probably Damaging | 0.761 | Possibly Damaging | 2.75 | Benign | 0.84 | Tolerated | 0.1328 | 0.1603 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.3094C>A | L1032M 2D AIThe SynGAP1 missense variant L1032M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995318 | Binding | 0.365 | 0.735 | 0.500 | -4.353 | Likely Benign | 0.219 | Likely Benign | Likely Benign | 0.064 | Likely Benign | -0.09 | Neutral | 0.995 | Probably Damaging | 0.892 | Possibly Damaging | 2.66 | Benign | 0.10 | Tolerated | 0.0935 | 0.4719 | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3094C>G | L1032V 2D AIThe SynGAP1 missense variant L1032V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and polyPhen‑2 HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995318 | Binding | 0.365 | 0.735 | 0.500 | -4.123 | Likely Benign | 0.176 | Likely Benign | Likely Benign | 0.075 | Likely Benign | 0.16 | Neutral | 0.889 | Possibly Damaging | 0.514 | Possibly Damaging | 2.78 | Benign | 0.78 | Tolerated | 0.1637 | 0.4353 | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||||||
| c.3095T>A | L1032Q 2D AIThe SynGAP1 missense variant L1032Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the aggregate evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995318 | Binding | 0.365 | 0.735 | 0.500 | -2.992 | Likely Benign | 0.467 | Ambiguous | Likely Benign | 0.134 | Likely Benign | -0.78 | Neutral | 0.995 | Probably Damaging | 0.892 | Possibly Damaging | 2.66 | Benign | 0.03 | Affected | 0.1217 | 0.1677 | -2 | -2 | -7.3 | 14.97 | |||||||||||||||||||||||||||||||||||||||
| c.3095T>C | L1032P 2D AIThe SynGAP1 missense variant L1032P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score all classify the change as benign or likely benign. AlphaMissense‑Optimized also predicts a benign outcome, whereas SIFT uniquely flags the variant as pathogenic. The AlphaMissense‑Default assessment is uncertain, and no Foldetta stability data are available. High‑accuracy analyses reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta results are missing, so they do not influence the interpretation. Overall, the majority of computational evidence supports a benign classification, which is consistent with the absence of a ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this conclusion does not contradict ClinVar status, as no ClinVar pathogenic claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995318 | Binding | 0.365 | 0.735 | 0.500 | -2.560 | Likely Benign | 0.449 | Ambiguous | Likely Benign | 0.142 | Likely Benign | -0.71 | Neutral | 0.012 | Benign | 0.017 | Benign | 2.64 | Benign | 0.05 | Affected | 0.3024 | 0.2330 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||||||
| c.3095T>G | L1032R 2D AIThe SynGAP1 missense variant L1032R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995318 | Binding | 0.365 | 0.735 | 0.500 | -2.658 | Likely Benign | 0.707 | Likely Pathogenic | Likely Benign | 0.099 | Likely Benign | -1.03 | Neutral | 0.995 | Probably Damaging | 0.892 | Possibly Damaging | 2.66 | Benign | 0.02 | Affected | 0.1350 | 0.1919 | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||||||
| c.3085C>A | Q1029K 2D AIThe SynGAP1 missense variant Q1029K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default remains uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta data is missing. Overall, the majority of evidence points to a benign impact for Q1029K, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -3.698 | Likely Benign | 0.516 | Ambiguous | Likely Benign | 0.075 | Likely Benign | -1.18 | Neutral | 0.771 | Possibly Damaging | 0.482 | Possibly Damaging | 2.79 | Benign | 1.00 | Tolerated | 0.1656 | 0.4196 | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||||||
| c.3085C>G | Q1029E 2D AIThe SynGAP1 missense variant Q1029E is reported in gnomAD (ID 6‑33443637‑C‑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 predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | 6-33443637-C-G | 17 | 1.05e-5 | -3.660 | Likely Benign | 0.281 | Likely Benign | Likely Benign | 0.044 | Likely Benign | -0.92 | Neutral | 0.625 | Possibly Damaging | 0.258 | Benign | 2.83 | Benign | 0.26 | Tolerated | 3.77 | 5 | 0.1327 | 0.2433 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||||||
| c.3086A>C | Q1029P 2D AIThe SynGAP1 missense variant Q1029P is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available for this variant. Overall, the consensus of all available predictions strongly supports a benign impact, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -2.940 | Likely Benign | 0.124 | Likely Benign | Likely Benign | 0.105 | Likely Benign | -1.23 | Neutral | 0.005 | Benign | 0.015 | Benign | 2.68 | Benign | 0.15 | Tolerated | 0.1966 | 0.4986 | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||||||
| c.3086A>G | Q1029R 2D AIThe SynGAP1 missense variant Q1029R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign; Foldetta results are unavailable. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, and this 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 | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -3.437 | Likely Benign | 0.420 | Ambiguous | Likely Benign | 0.073 | Likely Benign | -0.72 | Neutral | 0.961 | Probably Damaging | 0.677 | Possibly Damaging | 2.73 | Benign | 0.88 | Tolerated | 0.1377 | 0.2420 | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||||||
| c.3086A>T | Q1029L 2D AIThe SynGAP1 missense variant Q1029L 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. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). AlphaMissense‑Default remains uncertain, and Foldetta results are unavailable. High‑accuracy predictions therefore point to a benign impact: AlphaMissense‑Optimized is benign, SGM Consensus is benign, and no Foldetta data are available. Overall, the computational evidence indicates that the variant is most likely benign, and this assessment 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. | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -3.984 | Likely Benign | 0.364 | Ambiguous | Likely Benign | 0.067 | Likely Benign | -2.65 | Deleterious | 0.891 | Possibly Damaging | 0.587 | Possibly Damaging | 2.70 | Benign | 0.16 | Tolerated | 0.0685 | 0.5866 | -2 | -2 | 7.3 | -14.97 | ||||||||||||||||||||||||||||||||||||||||
| c.3087G>C | Q1029H 2D AIThe SynGAP1 missense variant Q1029H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments 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 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 | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -3.984 | Likely Benign | 0.308 | Likely Benign | Likely Benign | 0.041 | Likely Benign | -0.83 | Neutral | 0.989 | Probably Damaging | 0.879 | Possibly Damaging | 2.74 | Benign | 0.15 | Tolerated | 0.1268 | 0.4184 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3087G>T | Q1029H 2D AIThe SynGAP1 missense variant Q1029H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of the available 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 | 0.852992 | Disordered | 0.995643 | Binding | 0.375 | 0.734 | 0.500 | -3.984 | Likely Benign | 0.308 | Likely Benign | Likely Benign | 0.041 | Likely Benign | -0.83 | Neutral | 0.989 | Probably Damaging | 0.879 | Possibly Damaging | 2.74 | Benign | 0.15 | Tolerated | 0.1268 | 0.4184 | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3088C>A | H1030N 2D AIThe SynGAP1 missense variant H1030N is not reported in ClinVar and is absent from gnomAD. Consensus prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -3.454 | Likely Benign | 0.075 | Likely Benign | Likely Benign | 0.033 | Likely Benign | -0.88 | Neutral | 0.001 | Benign | 0.001 | Benign | 2.78 | Benign | 0.04 | Affected | 0.1553 | 0.3195 | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||||||
| c.3088C>G | H1030D 2D AIThe SynGAP1 missense variant H1030D is reported in gnomAD (variant ID 6‑33443640‑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, and AlphaMissense‑Optimized all predict benign. Only SIFT predicts a pathogenic effect, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | 6-33443640-C-G | 1 | 6.19e-7 | -3.500 | Likely Benign | 0.424 | Ambiguous | Likely Benign | 0.189 | Likely Benign | -0.85 | Neutral | 0.126 | Benign | 0.066 | Benign | 2.78 | Benign | 0.05 | Affected | 3.77 | 5 | 0.2273 | 0.2422 | -1 | 1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||||||
| c.3088C>T | H1030Y 2D AIThe SynGAP1 missense variant H1030Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for H1030Y, 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 | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -5.365 | Likely Benign | 0.268 | Likely Benign | Likely Benign | 0.026 | Likely Benign | -1.73 | Neutral | 0.812 | Possibly Damaging | 0.298 | Benign | 2.73 | Benign | 0.01 | Affected | 0.0874 | 0.4236 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||||||
| c.3089A>C | H1030P 2D AIThe SynGAP1 missense variant H1030P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that H1030P 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 | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -2.185 | Likely Benign | 0.148 | Likely Benign | Likely Benign | 0.154 | Likely Benign | -0.78 | Neutral | 0.812 | Possibly Damaging | 0.298 | Benign | 2.77 | Benign | 0.02 | Affected | 0.1872 | 0.4225 | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||||||
| c.3089A>G | H1030R 2D AIThe SynGAP1 missense variant H1030R is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -2.312 | Likely Benign | 0.340 | Likely Benign | Likely Benign | 0.031 | Likely Benign | -1.08 | Neutral | 0.224 | Benign | 0.066 | Benign | 2.85 | Benign | 0.06 | Tolerated | 0.1872 | 0.2955 | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||||||
| c.3089A>T | H1030L 2D AIThe SynGAP1 missense variant H1030L is 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that H1030L is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -3.513 | Likely Benign | 0.270 | Likely Benign | Likely Benign | 0.108 | Likely Benign | -2.35 | Neutral | 0.224 | Benign | 0.120 | Benign | 2.76 | Benign | 0.02 | Affected | 0.0968 | 0.5710 | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||||||
| c.3090C>A | H1030Q 2D AIThe SynGAP1 missense variant H1030Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -2.548 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.033 | Likely Benign | 0.01 | Neutral | 0.004 | Benign | 0.004 | Benign | 2.88 | Benign | 0.53 | Tolerated | 0.1538 | 0.4001 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3090C>G | H1030Q 2D AIThe SynGAP1 missense variant H1030Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.849326 | Disordered | 0.995856 | Binding | 0.375 | 0.735 | 0.500 | -2.548 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.033 | Likely Benign | 0.01 | Neutral | 0.004 | Benign | 0.004 | Benign | 2.88 | Benign | 0.53 | Tolerated | 0.1538 | 0.4001 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||||||
| c.3091A>C | M1031L 2D AIThe SynGAP1 missense variant M1031L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -2.213 | Likely Benign | 0.162 | Likely Benign | Likely Benign | 0.056 | Likely Benign | -0.82 | Neutral | 0.044 | Benign | 0.018 | Benign | 2.84 | Benign | 0.33 | Tolerated | 0.1220 | 0.4050 | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3091A>G | M1031V 2D AIThe SynGAP1 missense variant M1031V is catalogued in gnomAD (ID 6‑33443643‑A‑G) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently scores the variant as benign. No pathogenic predictions are reported. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the uniform benign predictions and the lack of any ClinVar pathogenic classification, the variant is most likely benign and does not contradict existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | 6-33443643-A-G | 7 | 4.34e-6 | -2.815 | Likely Benign | 0.198 | Likely Benign | Likely Benign | 0.054 | Likely Benign | -0.81 | Neutral | 0.002 | Benign | 0.003 | Benign | 2.72 | Benign | 0.44 | Tolerated | 3.77 | 5 | 0.2305 | 0.3388 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||||||||||||||
| c.3091A>T | M1031L 2D AIThe SynGAP1 missense variant M1031L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -2.213 | Likely Benign | 0.162 | Likely Benign | Likely Benign | 0.056 | Likely Benign | -0.82 | Neutral | 0.044 | Benign | 0.018 | Benign | 2.84 | Benign | 0.33 | Tolerated | 0.1220 | 0.4050 | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3092T>A | M1031K 2D AIThe SynGAP1 missense variant M1031K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant 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 | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -1.940 | Likely Benign | 0.709 | Likely Pathogenic | Likely Benign | 0.114 | Likely Benign | -0.80 | Neutral | 0.325 | Benign | 0.098 | Benign | 2.66 | Benign | 0.18 | Tolerated | 0.1224 | 0.1412 | 0 | -1 | -5.8 | -3.02 | |||||||||||||||||||||||||||||||||||||||
| c.3092T>C | M1031T 2D AIThe SynGAP1 missense variant M1031T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443644‑T‑C). In silico prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is AlphaMissense‑Default, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus is “Likely Benign,” and Foldetta data are not available. **Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | Uncertain | 1 | 6-33443644-T-C | 2 | 1.24e-6 | -1.863 | Likely Benign | 0.540 | Ambiguous | Likely Benign | 0.085 | Likely Benign | -0.24 | Neutral | 0.002 | Benign | 0.005 | Benign | 2.67 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0.1587 | 0.2264 | -1 | -1 | -2.6 | -30.09 | ||||||||||||||||||||||||||||||||
| c.3092T>G | M1031R 2D AIThe SynGAP1 missense variant M1031R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for M1031R, 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 | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -1.365 | Likely Benign | 0.673 | Likely Pathogenic | Likely Benign | 0.117 | Likely Benign | -0.85 | Neutral | 0.325 | Benign | 0.129 | Benign | 2.64 | Benign | 0.12 | Tolerated | 0.1368 | 0.1212 | 0 | -1 | -6.4 | 24.99 | |||||||||||||||||||||||||||||||||||||||
| c.3093G>A | M1031I 2D AIThe SynGAP1 missense variant M1031I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a benign impact for M1031I. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -3.312 | Likely Benign | 0.739 | Likely Pathogenic | Likely Benign | 0.026 | Likely Benign | -0.99 | Neutral | 0.095 | Benign | 0.027 | Benign | 2.71 | Benign | 0.25 | Tolerated | 0.1128 | 0.3324 | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3093G>C | M1031I 2D AIThe SynGAP1 missense variant M1031I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a benign impact for M1031I. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -3.312 | Likely Benign | 0.739 | Likely Pathogenic | Likely Benign | 0.025 | Likely Benign | -0.99 | Neutral | 0.095 | Benign | 0.027 | Benign | 2.71 | Benign | 0.25 | Tolerated | 0.1128 | 0.3324 | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||||||
| c.3093G>T | M1031I 2D AIThe SynGAP1 missense variant M1031I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a benign impact for M1031I. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.865454 | Disordered | 0.995959 | Binding | 0.340 | 0.736 | 0.500 | -3.312 | Likely Benign | 0.739 | Likely Pathogenic | Likely Benign | 0.026 | Likely Benign | -0.99 | Neutral | 0.095 | Benign | 0.027 | Benign | 2.71 | Benign | 0.25 | Tolerated | 0.1128 | 0.3324 | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||||||
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