Table of SynGAP1 Isoform α2 (UniProt Q96PV0-1) Missense Variants.
| c.dna | Variant | SGM Consensus | Domain | IUPred2 | ANCHOR2 | AlphaFold | MobiDB | ClinVar | gnomAD | ESM1b | AlphaMissense | REVEL | PSMutPred | FoldX | Rosetta | Foldetta | PremPS | PROVEAN | PolyPhen-2 HumDiv | PolyPhen-2 HumVar | FATHMM | SIFT | PAM | Physical | SASA | Normalized B-factor backbone | Normalized B-factor sidechain | SynGAP Structural Annotation | DOI | ||||||||||||||||||||||||||||||||||||||
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| Score | Prediction | Score | Prediction | pLDDT | disorder | disorder | Clinical Status | Review | Subm. | ID | Allele count | Allele freq. | LLR score | Prediction | Pathogenicity | Class | Optimized | Score | Prediction | IP RF | SP RF | Prediction | Average ΔΔG | Prediction | StdDev | ΔΔG | Prediction | ΔΔG | Prediction | ΔΔG | Prediction | Score | Prediction | pph2_prob | Prediction | pph2_prob | Prediction | Nervous System Score | Prediction | Prediction | Status | Conservation | Sequences | PAM250 | PAM120 | Hydropathy Δ | MW Δ | Average | Δ | Δ | StdDev | Δ | StdDev | Secondary | Tertiary bonds | Inside out | GAP-Ras interface | At membrane | No effect | MD Alert | Verdict | Description | |||||
| c.2521G>T | V841L 2D  AIThe SynGAP1 missense variant V841L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.622677 | Disordered | 0.616495 | Binding | 0.261 | 0.873 | 0.125 | -7.924 | In-Between | 0.514 | Ambiguous | Likely Benign | 0.157 | Likely Benign | 0.0850 | 0.4233 | -0.01 | Neutral | 0.992 | Probably Damaging | 0.989 | Probably Damaging | 2.85 | Benign | 0.56 | Tolerated | 2 | 1 | -0.4 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2522T>A | V841E 2D  AIThe SynGAP1 missense variant V841E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that V841E 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 | 0.622677 | Disordered | 0.616495 | Binding | 0.261 | 0.873 | 0.125 | -13.750 | Likely Pathogenic | 0.976 | Likely Pathogenic | Likely Pathogenic | 0.292 | Likely Benign | 0.0939 | 0.1656 | -3.13 | Deleterious | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.52 | Benign | 0.00 | Affected | -2 | -2 | -7.7 | 29.98 | |||||||||||||||||||||||||||||||||||
| c.2522T>C | V841A 2D  AIThe SynGAP1 missense variant V841A (ClinVar ID 1395978.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443074‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool reports an uncertain outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (two pathogenic, two benign) and is therefore inconclusive. No Foldetta stability assessment is available for this variant. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.622677 | Disordered | 0.616495 | Binding | 0.261 | 0.873 | 0.125 | Uncertain | 1 | 6-33443074-T-C | 3 | 1.86e-6 | -8.152 | Likely Pathogenic | 0.901 | Likely Pathogenic | Ambiguous | 0.183 | Likely Benign | 0.3069 | 0.2106 | -2.13 | Neutral | 0.992 | Probably Damaging | 0.989 | Probably Damaging | 2.57 | Benign | 0.02 | Affected | 3.77 | 5 | 0 | 0 | -2.4 | -28.05 | |||||||||||||||||||||||||||||
| c.2522T>G | V841G 2D  AIThe SynGAP1 missense variant V841G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, whereas the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity. 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 V841G, 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. | 0.622677 | Disordered | 0.616495 | Binding | 0.261 | 0.873 | 0.125 | -10.054 | Likely Pathogenic | 0.913 | Likely Pathogenic | Ambiguous | 0.288 | Likely Benign | 0.2351 | 0.2422 | -4.11 | Deleterious | 0.997 | Probably Damaging | 0.999 | Probably Damaging | 2.51 | Benign | 0.00 | Affected | -1 | -3 | -4.6 | -42.08 | ||||||||||||||||||||||||||||||||||||
| c.2620C>A | Q874K 2D  AIThe SynGAP1 missense variant Q874K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -6.379 | Likely Benign | 0.604 | Likely Pathogenic | Likely Benign | 0.169 | Likely Benign | 0.2008 | 0.4893 | -2.35 | Neutral | 0.963 | Probably Damaging | 0.973 | Probably Damaging | 2.73 | Benign | 0.00 | Affected | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.2620C>G | Q874E 2D  AIThe SynGAP1 missense variant Q874E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for Q874E, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -4.576 | Likely Benign | 0.197 | Likely Benign | Likely Benign | 0.193 | Likely Benign | 0.1489 | 0.3577 | -1.95 | Neutral | 0.963 | Probably Damaging | 0.973 | Probably Damaging | 2.73 | Benign | 0.00 | Affected | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.2621A>C | Q874P 2D  AIThe SynGAP1 missense variant Q874P is reported in gnomAD (ID 6‑33443173‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar classification (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 | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | 6-33443173-A-C | 9 | 5.58e-6 | -4.622 | Likely Benign | 0.125 | Likely Benign | Likely Benign | 0.219 | Likely Benign | 0.2373 | 0.5911 | -2.89 | Deleterious | 0.996 | Probably Damaging | 0.992 | Probably Damaging | 2.77 | Benign | 0.00 | Affected | 3.77 | 5 | -1 | 0 | 1.9 | -31.01 | ||||||||||||||||||||||||||||||
| c.2621A>G | Q874R 2D  AIThe SynGAP1 missense variant Q874R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts a benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -4.834 | Likely Benign | 0.527 | Ambiguous | Likely Benign | 0.200 | Likely Benign | 0.1619 | 0.2924 | -2.33 | Neutral | 0.985 | Probably Damaging | 0.982 | Probably Damaging | 2.69 | Benign | 0.00 | Affected | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.2621A>T | Q874L 2D  AIThe SynGAP1 missense variant Q874L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -6.084 | Likely Benign | 0.608 | Likely Pathogenic | Likely Benign | 0.199 | Likely Benign | 0.0828 | 0.6595 | -3.39 | Deleterious | 0.985 | Probably Damaging | 0.982 | Probably Damaging | 2.67 | Benign | 0.00 | Affected | -2 | -2 | 7.3 | -14.97 | ||||||||||||||||||||||||||||||||||||
| c.2622G>C | Q874H 2D  AIThe SynGAP1 missense variant Q874H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the balance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -4.658 | Likely Benign | 0.543 | Ambiguous | Likely Benign | 0.236 | Likely Benign | 0.1588 | 0.5088 | -2.90 | Deleterious | 0.996 | Probably Damaging | 0.995 | Probably Damaging | 2.65 | Benign | 0.00 | Affected | 3 | 0 | 0.3 | 9.01 | ||||||||||||||||||||||||||||||||||||
| c.2622G>T | Q874H 2D AIThe SynGAP1 missense variant Q874H has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.490133 | Structured | 0.635258 | Binding | 0.289 | 0.873 | 0.250 | -4.658 | Likely Benign | 0.543 | Ambiguous | Likely Benign | 0.236 | Likely Benign | 0.1588 | 0.5088 | -2.90 | Deleterious | 0.996 | Probably Damaging | 0.995 | Probably Damaging | 2.65 | Benign | 0.00 | Affected | 3 | 0 | 0.3 | 9.01 | ||||||||||||||||||||||||||||||||||||
| c.268G>A | V90M 2D  AIThe SynGAP1 missense variant V90M is listed in gnomAD (6‑33425876‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | 6-33425876-G-A | 1 | 6.20e-7 | -5.017 | Likely Benign | 0.463 | Ambiguous | Likely Benign | 0.053 | Likely Benign | 0.1221 | 0.4393 | -0.15 | Neutral | 0.872 | Possibly Damaging | 0.162 | Benign | 3.98 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | -2.3 | 32.06 | ||||||||||||||||||||||||||||||
| c.268G>C | V90L 2D AIThe SynGAP1 missense variant V90L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while SIFT uniquely predicts it as pathogenic. The consensus from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus also indicates Likely Benign, and Foldetta data are unavailable. With the majority of evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | -3.676 | Likely Benign | 0.522 | Ambiguous | Likely Benign | 0.056 | Likely Benign | 0.1334 | 0.4487 | -0.24 | Neutral | 0.103 | Benign | 0.015 | Benign | 4.02 | Benign | 0.00 | Affected | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.268G>T | V90L 2D AIThe SynGAP1 missense variant V90L 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 indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for V90L, 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 | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | -3.676 | Likely Benign | 0.522 | Ambiguous | Likely Benign | 0.056 | Likely Benign | 0.1334 | 0.4487 | -0.24 | Neutral | 0.103 | Benign | 0.015 | Benign | 4.02 | Benign | 0.00 | Affected | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.269T>A | V90E 2D AIThe SynGAP1 missense variant V90E is listed in ClinVar (ID 971665.0) with an uncertain significance status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only two tools—SIFT and AlphaMissense‑Default—suggest a pathogenic outcome. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains benign, and the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability assessment is available for this variant. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | Uncertain | 1 | -4.079 | Likely Benign | 0.703 | Likely Pathogenic | Likely Benign | 0.108 | Likely Benign | 0.1323 | 0.2233 | -0.38 | Neutral | 0.001 | Benign | 0.000 | Benign | 4.00 | Benign | 0.00 | Affected | 4.32 | 1 | -2 | -2 | -7.7 | 29.98 | |||||||||||||||||||||||||||||||
| c.269T>C | V90A 2D AIThe SynGAP1 missense variant V90A 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. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that V90A 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 | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | -0.984 | Likely Benign | 0.288 | Likely Benign | Likely Benign | 0.055 | Likely Benign | 0.3129 | 0.3154 | 0.27 | Neutral | 0.053 | Benign | 0.008 | Benign | 4.11 | Benign | 0.00 | Affected | 0 | 0 | -2.4 | -28.05 | |||||||||||||||||||||||||||||||||||
| c.269T>G | V90G 2D AIThe SynGAP1 missense variant V90G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign verdict. 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. | 0.570702 | Disordered | 0.542047 | Binding | 0.343 | 0.873 | 0.500 | -2.617 | Likely Benign | 0.358 | Ambiguous | Likely Benign | 0.094 | Likely Benign | 0.2047 | 0.2936 | -0.55 | Neutral | 0.024 | Benign | 0.208 | Benign | 4.00 | Benign | 0.00 | Affected | -1 | -3 | -4.6 | -42.08 | ||||||||||||||||||||||||||||||||||||
| c.3913A>C | T1305P 2D  AIThe SynGAP1 missense variant T1305P is not reported 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 | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | -1.882 | Likely Benign | 0.058 | Likely Benign | Likely Benign | 0.204 | Likely Benign | 0.2157 | 0.5386 | -1.41 | Neutral | 0.027 | Benign | 0.114 | Benign | 2.86 | Benign | 0.03 | Affected | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||
| c.3913A>G | T1305A 2D  AIThe SynGAP1 missense variant T1305A is listed in ClinVar (ID 411587.0) with an “Uncertain” clinical significance and is present in the gnomAD database (variant ID 6‑33451787‑A‑G). All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely pathogenic outcome. High‑accuracy assessments reinforce this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, 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 | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | Conflicting | 4 | 6-33451787-A-G | 30 | 1.86e-5 | -2.692 | Likely Benign | 0.055 | Likely Benign | Likely Benign | 0.069 | Likely Benign | 0.4533 | 0.4746 | 1.74 | Neutral | 0.000 | Benign | 0.001 | Benign | 3.24 | Benign | 1.00 | Tolerated | 3.77 | 5 | 1 | 0 | 2.5 | -30.03 | ||||||||||||||||||||||||||||
| c.3913A>T | T1305S 2D  AIThe SynGAP1 missense variant T1305S 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 | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | -2.813 | Likely Benign | 0.074 | Likely Benign | Likely Benign | 0.053 | Likely Benign | 0.3683 | 0.4988 | 0.20 | Neutral | 0.003 | Benign | 0.026 | Benign | 2.83 | Benign | 0.08 | Tolerated | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.3914C>A | T1305K 2D  AIThe SynGAP1 missense variant T1305K 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 reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for T1305K, 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 | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | -4.289 | Likely Benign | 0.299 | Likely Benign | Likely Benign | 0.164 | Likely Benign | 0.1290 | 0.3532 | -1.33 | Neutral | 0.027 | Benign | 0.042 | Benign | 2.77 | Benign | 0.01 | Affected | 0 | -1 | -3.2 | 27.07 | |||||||||||||||||||||||||||||||||||
| c.3914C>G | T1305R 2D  AIThe SynGAP1 missense variant T1305R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | -2.945 | Likely Benign | 0.194 | Likely Benign | Likely Benign | 0.220 | Likely Benign | 0.1115 | 0.3214 | -1.33 | Neutral | 0.027 | Benign | 0.114 | Benign | 2.75 | Benign | 0.01 | Affected | -1 | -1 | -3.8 | 55.08 | |||||||||||||||||||||||||||||||||||
| c.3914C>T | T1305I 2D  AIThe SynGAP1 missense variant T1305I 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 call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.791621 | Disordered | 0.894658 | Binding | 0.390 | 0.873 | 0.875 | -4.202 | Likely Benign | 0.221 | Likely Benign | Likely Benign | 0.154 | Likely Benign | 0.0923 | 0.6149 | -1.35 | Neutral | 0.027 | Benign | 0.063 | Benign | 2.77 | Benign | 0.02 | Affected | 0 | -1 | 5.2 | 12.05 | |||||||||||||||||||||||||||||||||||
| c.2296T>A | S766T 2D  AIThe SynGAP1 missense variant S766T is not reported 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. 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 | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | -4.923 | Likely Benign | 0.190 | Likely Benign | Likely Benign | 0.072 | Likely Benign | 0.1461 | 0.6511 | -1.25 | Neutral | 0.790 | Possibly Damaging | 0.433 | Benign | 4.15 | Benign | 0.02 | Affected | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2296T>C | S766P 2D  AIThe SynGAP1 missense variant S766P is reported in gnomAD (ID 6‑33442454‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while SIFT uniquely predicts it as pathogenic. The remaining tools, ESM1b and AlphaMissense‑Default, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | 6-33442454-T-C | 1 | 1.28e-6 | -7.343 | In-Between | 0.374 | Ambiguous | Likely Benign | 0.193 | Likely Benign | 0.2216 | 0.5862 | -0.91 | Neutral | 0.006 | Benign | 0.013 | Benign | 4.07 | Benign | 0.01 | Affected | 3.64 | 6 | -1 | 1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||
| c.2296T>G | S766A 2D  AIThe SynGAP1 missense variant S766A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | -6.115 | Likely Benign | 0.186 | Likely Benign | Likely Benign | 0.055 | Likely Benign | 0.5059 | 0.5705 | Strenghten | -0.98 | Neutral | 0.447 | Benign | 0.198 | Benign | 4.17 | Benign | 0.02 | Affected | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||
| c.2297C>A | S766Y 2D  AIThe SynGAP1 missense variant S766Y is reported in gnomAD (ID 6‑33442455‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) predicts pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | 6-33442455-C-A | -8.636 | Likely Pathogenic | 0.641 | Likely Pathogenic | Likely Benign | 0.222 | Likely Benign | 0.0794 | 0.5609 | -2.67 | Deleterious | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 4.09 | Benign | 0.00 | Affected | 3.64 | 6 | -2 | -3 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||
| c.2297C>G | S766C 2D  AIThe SynGAP1 missense variant S766C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S766C, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | -7.681 | In-Between | 0.326 | Likely Benign | Likely Benign | 0.192 | Likely Benign | 0.1049 | 0.6110 | -2.02 | Neutral | 0.997 | Probably Damaging | 0.889 | Possibly Damaging | 4.07 | Benign | 0.00 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2297C>T | S766F 2D  AIThe SynGAP1 missense variant S766F is listed in gnomAD (ID 6‑33442455‑C‑T) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.405110 | Structured | 0.923125 | Binding | 0.338 | 0.874 | 0.250 | 6-33442455-C-T | -8.944 | Likely Pathogenic | 0.709 | Likely Pathogenic | Likely Benign | 0.233 | Likely Benign | 0.0770 | 0.5887 | -2.87 | Deleterious | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 4.08 | Benign | 0.00 | Affected | 3.64 | 6 | -2 | -3 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||
| c.2488C>A | P830T 2D  AIThe SynGAP1 missense variant P830T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for P830T, 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 | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -4.697 | Likely Benign | 0.192 | Likely Benign | Likely Benign | 0.222 | Likely Benign | 0.1519 | 0.5970 | -3.56 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.67 | Benign | 0.02 | Affected | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||
| c.2488C>G | P830A 2D  AIThe SynGAP1 missense variant P830A 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, 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 the ClinVar status, which contains no entry for P830A. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -4.471 | Likely Benign | 0.146 | Likely Benign | Likely Benign | 0.202 | Likely Benign | 0.3534 | 0.5050 | -3.63 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.82 | Benign | 0.04 | Affected | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.2488C>T | P830S 2D  AIThe SynGAP1 missense variant P830S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 there is no ClinVar classification to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -4.629 | Likely Benign | 0.251 | Likely Benign | Likely Benign | 0.219 | Likely Benign | 0.3496 | 0.5450 | -3.23 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.70 | Benign | 0.28 | Tolerated | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||||||
| c.2489C>A | P830Q 2D  AIThe SynGAP1 missense variant P830Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments 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 | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -4.984 | Likely Benign | 0.304 | Likely Benign | Likely Benign | 0.257 | Likely Benign | 0.1396 | 0.4741 | -3.40 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.68 | Benign | 0.00 | Affected | 0 | -1 | -1.9 | 31.01 | |||||||||||||||||||||||||||||||||||
| c.2489C>G | P830R 2D  AIThe SynGAP1 missense variant P830R is not 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. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictors and the high‑accuracy consensus indicate a benign impact. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -5.919 | Likely Benign | 0.515 | Ambiguous | Likely Benign | 0.227 | Likely Benign | 0.1277 | 0.2984 | -3.51 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.72 | Benign | 0.00 | Affected | 0 | -2 | -2.9 | 59.07 | ||||||||||||||||||||||||||||||||||||
| c.2489C>T | P830L 2D  AIThe SynGAP1 missense variant P830L is not 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 predicts benign. Foldetta results are unavailable. Overall, the majority of reliable predictors lean toward 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. | 0.590140 | Disordered | 0.618152 | Binding | 0.333 | 0.874 | 0.500 | -3.990 | Likely Benign | 0.362 | Ambiguous | Likely Benign | 0.269 | Likely Benign | 0.2138 | 0.6631 | -5.31 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.65 | Benign | 0.00 | Affected | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||
| c.2491G>A | E831K 2D  AIThe SynGAP1 missense variant E831K is not reported 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, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools lean benign, but the high‑accuracy consensus and several individual pathogenic predictions suggest a pathogenic likelihood. Thus, the variant is most likely pathogenic based on the available 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. | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -7.447 | In-Between | 0.636 | Likely Pathogenic | Likely Benign | 0.167 | Likely Benign | 0.1989 | 0.6995 | -1.43 | Neutral | 0.625 | Possibly Damaging | 0.252 | Benign | 2.37 | Pathogenic | 0.07 | Tolerated | 0 | 1 | -0.4 | -0.94 | ||||||||||||||||||||||||||||||||||||
| c.2491G>C | E831Q 2D  AIThe SynGAP1 missense variant E831Q is not 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, favors a benign outcome (2 benign vs. 1 pathogenic). High‑accuracy methods give a benign prediction from AlphaMissense‑Optimized and a benign consensus from SGM; Foldetta results are unavailable. Overall, the available computational evidence points to a benign impact for E831Q, and this assessment does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -5.604 | Likely Benign | 0.349 | Ambiguous | Likely Benign | 0.147 | Likely Benign | 0.1022 | 0.7052 | -1.23 | Neutral | 0.891 | Possibly Damaging | 0.492 | Possibly Damaging | 2.36 | Pathogenic | 0.09 | Tolerated | 2 | 2 | 0.0 | -0.98 | ||||||||||||||||||||||||||||||||||||
| c.2492A>C | E831A 2D  AIThe SynGAP1 missense variant E831A is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, polyPhen‑2 HumVar, and ESM1b, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and FATHMM. AlphaMissense‑Default is uncertain, whereas AlphaMissense‑Optimized predicts benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools therefore give conflicting signals: AlphaMissense‑Optimized benign versus SGM Consensus pathogenic, with no Foldetta data. Overall, the bulk of predictions lean toward a benign effect, 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. | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -4.780 | Likely Benign | 0.429 | Ambiguous | Likely Benign | 0.115 | Likely Benign | 0.3845 | 0.6868 | -2.56 | Deleterious | 0.625 | Possibly Damaging | 0.315 | Benign | 2.36 | Pathogenic | 0.07 | Tolerated | 0 | -1 | 5.3 | -58.04 | ||||||||||||||||||||||||||||||||||||
| c.2492A>G | E831G 2D  AIThe SynGAP1 missense variant E831G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, SIFT, FATHMM). The high‑accuracy AlphaMissense‑Optimized model predicts a benign effect, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. No Foldetta stability assessment is available. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any existing ClinVar annotation, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -4.769 | Likely Benign | 0.305 | Likely Benign | Likely Benign | 0.119 | Likely Benign | 0.2924 | 0.6205 | -2.27 | Neutral | 0.625 | Possibly Damaging | 0.252 | Benign | 2.41 | Pathogenic | 0.04 | Affected | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||
| c.2492A>T | E831V 2D  AIThe SynGAP1 missense variant E831V is not reported in ClinVar and has no gnomAD allele. Prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls 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, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus indicates a likely pathogenic outcome, and Foldetta data are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -6.327 | Likely Benign | 0.629 | Likely Pathogenic | Likely Benign | 0.204 | Likely Benign | 0.0604 | 0.7407 | -3.43 | Deleterious | 0.891 | Possibly Damaging | 0.492 | Possibly Damaging | 2.32 | Pathogenic | 0.02 | Affected | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||
| c.2493G>C | E831D 2D  AIThe SynGAP1 missense variant E831D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443045‑G‑C). All available in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely‑pathogenic outcome. Grouping by agreement, the benign‑predicting tools comprise the entire set, while no pathogenic predictions are present. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign classification. Foldetta results are unavailable. Overall, the computational evidence strongly supports a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | Uncertain | 1 | 6-33443045-G-C | 1 | 6.19e-7 | -3.055 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.073 | Likely Benign | 0.1537 | 0.4530 | 1.23 | Neutral | 0.002 | Benign | 0.002 | Benign | 2.64 | Benign | 0.77 | Tolerated | 3.77 | 5 | 3 | 2 | 0.0 | -14.03 | ||||||||||||||||||||||||||||
| c.2493G>T | E831D 2D AIThe SynGAP1 missense variant E831D is not reported in ClinVar and is absent from gnomAD. 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 reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are not available. Based on the consensus of all predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.626927 | Disordered | 0.617732 | Binding | 0.319 | 0.874 | 0.375 | -3.055 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.073 | Likely Benign | 0.1537 | 0.4530 | 1.23 | Neutral | 0.002 | Benign | 0.002 | Benign | 2.64 | Benign | 0.77 | Tolerated | 3.77 | 5 | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||
| c.2635G>A | A879T 2D  AIThe SynGAP1 missense variant A879T is reported in gnomAD (6-33443187‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Taken together, the majority of evidence points to a benign impact for A879T, 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 | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | 6-33443187-G-A | 3 | 1.86e-6 | -5.161 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.042 | Likely Benign | 0.1292 | 0.6754 | -0.98 | Neutral | 0.872 | Possibly Damaging | 0.580 | Possibly Damaging | 2.66 | Benign | 0.19 | Tolerated | 3.77 | 5 | 0 | 1 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||
| c.2635G>C | A879P 2D  AIThe SynGAP1 missense variant A879P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that A879P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | -4.317 | Likely Benign | 0.114 | Likely Benign | Likely Benign | 0.151 | Likely Benign | 0.1713 | 0.5004 | -1.16 | Neutral | 0.986 | Probably Damaging | 0.825 | Possibly Damaging | 2.61 | Benign | 0.23 | Tolerated | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.2635G>T | A879S 2D  AIThe SynGAP1 missense variant A879S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | -3.406 | Likely Benign | 0.086 | Likely Benign | Likely Benign | 0.091 | Likely Benign | 0.2469 | 0.5266 | -0.26 | Neutral | 0.580 | Possibly Damaging | 0.324 | Benign | 2.68 | Benign | 0.44 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.2635_2636delinsAA | A879K 2D  AIThe SynGAP1 missense variant A879K is listed in ClinVar (ID 575856.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this consensus aligns with the ClinVar designation, with no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | Likely Benign | 1 | -5.877 | Likely Benign | 0.757 | Likely Pathogenic | Likely Benign | 0.0930 | 0.2569 | -0.71 | Neutral | 0.969 | Probably Damaging | 0.593 | Possibly Damaging | 2.69 | Benign | 0.21 | Tolerated | 3.77 | 5 | -1 | -1 | -5.7 | 57.10 | |||||||||||||||||||||||||||||||||
| c.2636C>A | A879E 2D  AIThe SynGAP1 missense variant A879E is reported in gnomAD (variant ID 6‑33443188‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy predictions specifically show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data is missing. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | 6-33443188-C-A | 1 | 6.20e-7 | -3.786 | Likely Benign | 0.503 | Ambiguous | Likely Benign | 0.070 | Likely Benign | 0.1120 | 0.1903 | -0.27 | Neutral | 0.872 | Possibly Damaging | 0.659 | Possibly Damaging | 2.70 | Benign | 0.27 | Tolerated | 3.77 | 5 | -1 | 0 | -5.3 | 58.04 | ||||||||||||||||||||||||||||||
| c.2636C>G | A879G 2D  AIThe SynGAP1 missense variant A879G is reported in gnomAD (variant ID 6-33443188-C-G) but has no ClinVar entry. Functional prediction tools uniformly classify the change 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. 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, so they do not influence the assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | 6-33443188-C-G | 1 | 6.20e-7 | -3.924 | Likely Benign | 0.085 | Likely Benign | Likely Benign | 0.054 | Likely Benign | 0.2214 | 0.4362 | -0.43 | Neutral | 0.001 | Benign | 0.007 | Benign | 2.69 | Benign | 0.43 | Tolerated | 3.77 | 5 | 0 | 1 | -2.2 | -14.03 | ||||||||||||||||||||||||||||||
| c.2636C>T | A879V 2D  AIThe SynGAP1 missense variant A879V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.608892 | Disordered | 0.622695 | Binding | 0.277 | 0.874 | 0.250 | -6.177 | Likely Benign | 0.152 | Likely Benign | Likely Benign | 0.065 | Likely Benign | 0.1003 | 0.6293 | -1.46 | Neutral | 0.872 | Possibly Damaging | 0.580 | Possibly Damaging | 2.64 | Benign | 0.19 | Tolerated | 0 | 0 | 2.4 | 28.05 | |||||||||||||||||||||||||||||||||||
| c.2638G>A | A880T 2D AIThe SynGAP1 missense variant A880T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | -4.594 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.097 | Likely Benign | 0.1229 | 0.6396 | -0.75 | Neutral | 0.761 | Possibly Damaging | 0.399 | Benign | 2.61 | Benign | 0.29 | Tolerated | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.2638G>C | A880P 2D AIThe SynGAP1 missense variant A880P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | -3.671 | Likely Benign | 0.105 | Likely Benign | Likely Benign | 0.098 | Likely Benign | 0.1744 | 0.4106 | -0.55 | Neutral | 0.971 | Probably Damaging | 0.693 | Possibly Damaging | 2.61 | Benign | 0.11 | Tolerated | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.2638G>T | A880S 2D AIThe SynGAP1 missense variant A880S 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 | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | -3.149 | Likely Benign | 0.076 | Likely Benign | Likely Benign | 0.092 | Likely Benign | 0.2504 | 0.5108 | -0.33 | Neutral | 0.393 | Benign | 0.187 | Benign | 2.63 | Benign | 0.10 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.2639C>A | A880D 2D  AIThe SynGAP1 missense variant A880D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely benign outcome, and no Foldetta stability result is available. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | -4.571 | Likely Benign | 0.493 | Ambiguous | Likely Benign | 0.127 | Likely Benign | 0.1664 | 0.1904 | -1.29 | Neutral | 0.918 | Possibly Damaging | 0.401 | Benign | 2.60 | Benign | 0.03 | Affected | 0 | -2 | -5.3 | 44.01 | |||||||||||||||||||||||||||||||||||
| c.2639C>G | A880G 2D AIThe SynGAP1 missense variant A880G is catalogued in gnomAD (ID 6‑33443191‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. Only SIFT classifies the change as pathogenic, representing a single discordant signal. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus likewise reports likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of the majority of tools, including the high‑accuracy methods, 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 | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | 6-33443191-C-G | 2 | 1.24e-6 | -3.283 | Likely Benign | 0.071 | Likely Benign | Likely Benign | 0.049 | Likely Benign | 0.2136 | 0.3841 | -0.14 | Neutral | 0.002 | Benign | 0.007 | Benign | 2.62 | Benign | 0.04 | Affected | 3.77 | 5 | 0 | 1 | -2.2 | -14.03 | ||||||||||||||||||||||||||||||
| c.2639C>T | A880V 2D AIThe SynGAP1 missense variant A880V is reported in gnomAD (variant ID 6‑33443191‑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 the change as pathogenic, creating a single 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 (majority vote) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign impact for A880V, 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 | 0.703578 | Disordered | 0.621441 | Binding | 0.309 | 0.874 | 0.250 | 6-33443191-C-T | 1 | 6.20e-7 | -5.440 | Likely Benign | 0.121 | Likely Benign | Likely Benign | 0.095 | Likely Benign | 0.0947 | 0.5362 | -0.11 | Neutral | 0.761 | Possibly Damaging | 0.399 | Benign | 2.58 | Benign | 1.00 | Tolerated | 3.77 | 5 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||
| c.2641T>A | L881M 2D  AIThe SynGAP1 missense variant L881M is 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 exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -4.419 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.045 | Likely Benign | 0.0807 | 0.3997 | -0.31 | Neutral | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.49 | Pathogenic | 0.03 | Affected | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||
| c.2641T>G | L881V 2D  AIThe SynGAP1 missense variant L881V is not reported 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -3.961 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.061 | Likely Benign | 0.1599 | 0.3053 | -0.29 | Neutral | 0.790 | Possibly Damaging | 0.266 | Benign | 2.60 | Benign | 0.39 | Tolerated | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2642T>C | L881S 2D  AIThe SynGAP1 missense variant L881S is not reported 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 for the L881S 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 | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -3.063 | Likely Benign | 0.169 | Likely Benign | Likely Benign | 0.051 | Likely Benign | 0.3363 | 0.0850 | -0.49 | Neutral | 0.068 | Benign | 0.012 | Benign | 2.49 | Pathogenic | 0.00 | Affected | -3 | -2 | -4.6 | -26.08 | |||||||||||||||||||||||||||||||||||
| c.2642T>G | L881W 2D  AIThe SynGAP1 missense variant L881W is not reported 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 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 | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -6.646 | Likely Benign | 0.231 | Likely Benign | Likely Benign | 0.075 | Likely Benign | 0.0662 | 0.3288 | -0.96 | Neutral | 0.014 | Benign | 0.008 | Benign | 2.44 | Pathogenic | 0.00 | Affected | -2 | -2 | -4.7 | 73.05 | |||||||||||||||||||||||||||||||||||
| c.2643G>C | L881F 2D  AIThe SynGAP1 missense variant L881F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for L881F, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -5.759 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.044 | Likely Benign | 0.0711 | 0.3415 | -0.87 | Neutral | 0.818 | Possibly Damaging | 0.360 | Benign | 2.48 | Pathogenic | 0.02 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||
| c.2643G>T | L881F 2D AIThe SynGAP1 missense variant L881F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for L881F, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.703578 | Disordered | 0.629350 | Binding | 0.299 | 0.874 | 0.250 | -5.759 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.044 | Likely Benign | 0.0711 | 0.3415 | -0.87 | Neutral | 0.818 | Possibly Damaging | 0.360 | Benign | 2.48 | Pathogenic | 0.02 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||
| c.274G>A | G92R 2D  AIThe SynGAP1 missense variant G92R is listed in gnomAD (6-33425882‑G‑A) but has no ClinVar entry. Functional 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, reports 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 preponderance of evidence from multiple independent predictors and the consensus score points to a benign classification. 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 | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | 6-33425882-G-A | 1 | 6.20e-7 | -2.909 | Likely Benign | 0.876 | Likely Pathogenic | Ambiguous | 0.139 | Likely Benign | 0.1041 | 0.4605 | -2.38 | Neutral | 0.999 | Probably Damaging | 0.979 | Probably Damaging | 4.01 | Benign | 0.00 | Affected | 4.32 | 1 | -2 | -3 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||
| c.274G>C | G92R 2D AIThe SynGAP1 missense variant G92R is not reported 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 results are unavailable. Overall, the majority of high‑confidence tools and the consensus prediction lean toward a benign interpretation, with no conflict with ClinVar status. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | -2.909 | Likely Benign | 0.876 | Likely Pathogenic | Ambiguous | 0.139 | Likely Benign | 0.1041 | 0.4605 | -2.38 | Neutral | 0.999 | Probably Damaging | 0.979 | Probably Damaging | 4.01 | Benign | 0.00 | Affected | 4.32 | 1 | -2 | -3 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||
| c.274G>T | G92W 2D  AIThe SynGAP1 missense variant G92W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) suggest a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | -6.502 | Likely Benign | 0.789 | Likely Pathogenic | Ambiguous | 0.224 | Likely Benign | 0.0640 | 0.4546 | -2.61 | Deleterious | 1.000 | Probably Damaging | 0.979 | Probably Damaging | 3.95 | Benign | 0.00 | Affected | -7 | -2 | -0.5 | 129.16 | ||||||||||||||||||||||||||||||||||||
| c.275G>A | G92E 2D  AIThe SynGAP1 missense variant G92E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict 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 | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | -3.240 | Likely Benign | 0.651 | Likely Pathogenic | Likely Benign | 0.156 | Likely Benign | 0.1521 | 0.4426 | -2.27 | Neutral | 0.999 | Probably Damaging | 0.972 | Probably Damaging | 4.07 | Benign | 0.00 | Affected | 0 | -2 | -3.1 | 72.06 | |||||||||||||||||||||||||||||||||||
| c.275G>C | G92A 2D  AIThe SynGAP1 missense variant G92A 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 further support a benign classification: AlphaMissense‑Optimized returns “Benign” and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates “Likely Benign.” No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G92A, 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 | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | -4.044 | Likely Benign | 0.219 | Likely Benign | Likely Benign | 0.080 | Likely Benign | 0.3922 | 0.4930 | -1.53 | Neutral | 0.996 | Probably Damaging | 0.910 | Probably Damaging | 4.08 | Benign | 0.00 | Affected | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.275G>T | G92V 2D  AIThe SynGAP1 missense variant G92V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact for G92V, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.537848 | Binding | 0.337 | 0.874 | 0.625 | -4.627 | Likely Benign | 0.338 | Likely Benign | Likely Benign | 0.164 | Likely Benign | 0.1171 | 0.4363 | -2.62 | Deleterious | 0.999 | Probably Damaging | 0.972 | Probably Damaging | 4.00 | Benign | 0.00 | Affected | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| c.277C>G | R93G 2D  AIThe SynGAP1 missense variant R93G is listed in ClinVar (ID 2504251.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the same set of predictors) labels it “Likely Benign”; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that R93G is most likely benign, which does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.675549 | Disordered | 0.549151 | Binding | 0.290 | 0.874 | 0.625 | Uncertain | 1 | -2.674 | Likely Benign | 0.400 | Ambiguous | Likely Benign | 0.093 | Likely Benign | 0.3809 | 0.3814 | -1.69 | Neutral | 0.103 | Benign | 0.019 | Benign | 3.99 | Benign | 0.00 | Affected | 4.32 | 1 | -2 | -3 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||
| c.277C>T | R93W 2D  AIThe SynGAP1 missense variant R93W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R93W, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.675549 | Disordered | 0.549151 | Binding | 0.290 | 0.874 | 0.625 | -5.652 | Likely Benign | 0.514 | Ambiguous | Likely Benign | 0.094 | Likely Benign | 0.1413 | 0.3835 | -2.22 | Neutral | 0.981 | Probably Damaging | 0.257 | Benign | 3.96 | Benign | 0.00 | Affected | 2 | -3 | 3.6 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.278G>A | R93Q 2D  AIThe SynGAP1 missense variant R93Q is not reported 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 results are not available for this variant. Overall, the majority of evidence points to a benign effect; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.675549 | Disordered | 0.549151 | Binding | 0.290 | 0.874 | 0.625 | -3.938 | Likely Benign | 0.167 | Likely Benign | Likely Benign | 0.074 | Likely Benign | 0.3568 | 0.2669 | -0.38 | Neutral | 0.203 | Benign | 0.006 | Benign | 4.14 | Benign | 0.00 | Affected | 1 | 1 | 1.0 | -28.06 | |||||||||||||||||||||||||||||||||||
| c.278G>C | R93P 2D  AIThe SynGAP1 missense variant R93P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.675549 | Disordered | 0.549151 | Binding | 0.290 | 0.874 | 0.625 | -3.164 | Likely Benign | 0.473 | Ambiguous | Likely Benign | 0.121 | Likely Benign | 0.2200 | 0.4844 | -0.32 | Neutral | 0.361 | Benign | 0.038 | Benign | 3.99 | Benign | 0.00 | Affected | 0 | -2 | 2.9 | -59.07 | |||||||||||||||||||||||||||||||||||
| c.278G>T | R93L 2D  AIThe SynGAP1 R93L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to 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 | 0.675549 | Disordered | 0.549151 | Binding | 0.290 | 0.874 | 0.625 | -2.850 | Likely Benign | 0.425 | Ambiguous | Likely Benign | 0.064 | Likely Benign | 0.2197 | 0.4861 | -1.72 | Neutral | 0.103 | Benign | 0.019 | Benign | 4.00 | Benign | 0.00 | Affected | -3 | -2 | 8.3 | -43.03 | |||||||||||||||||||||||||||||||||||
| c.2806G>A | A936T 2D AIThe SynGAP1 missense variant A936T is catalogued in gnomAD (ID 6‑33443358‑G‑A) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the change as benign. No pathogenic predictions are reported. 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 outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign effect, and this conclusion does not contradict any ClinVar status (none). 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 | 6-33443358-G-A | 1 | 6.20e-7 | -4.540 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.047 | Likely Benign | 0.1693 | 0.7003 | -0.50 | Neutral | 0.051 | Benign | 0.033 | Benign | 2.67 | Benign | 0.09 | Tolerated | 3.77 | 5 | 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 | 0.2043 | 0.6109 | -1.28 | Neutral | 0.012 | Benign | 0.011 | Benign | 2.46 | Pathogenic | 0.06 | Tolerated | 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 | 0.2675 | 0.5300 | -0.07 | Neutral | 0.022 | Benign | 0.008 | Benign | 2.53 | Benign | 0.11 | Tolerated | 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 | 0.1778 | 0.1660 | -1.63 | Neutral | 0.801 | Possibly Damaging | 0.339 | Benign | 2.48 | Pathogenic | 0.02 | Affected | 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 | 0.2380 | 0.4529 | -1.34 | Neutral | 0.454 | Possibly Damaging | 0.192 | Benign | 2.48 | Pathogenic | 0.12 | Tolerated | 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 | 0.1586 | 0.6921 | -1.58 | Neutral | 0.801 | Possibly Damaging | 0.192 | Benign | 2.48 | Pathogenic | 0.19 | Tolerated | 3.77 | 5 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||
| c.295G>A | E99K 2D AIThe SynGAP1 E99K 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar reporting, 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 | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -4.746 | Likely Benign | 0.678 | Likely Pathogenic | Likely Benign | 0.071 | Likely Benign | 0.2752 | 0.8149 | -0.88 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.14 | Benign | 0.00 | Affected | 0 | 1 | -0.4 | -0.94 | |||||||||||||||||||||||||||||||||||
| c.295G>C | E99Q 2D AIThe SynGAP1 missense variant E99Q is reported in gnomAD (6-33425903‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑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 E99Q, 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 | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | 6-33425903-G-C | 1 | 6.20e-7 | -3.675 | Likely Benign | 0.325 | Likely Benign | Likely Benign | 0.056 | Likely Benign | 0.1672 | 0.7727 | -0.82 | Neutral | 0.001 | Benign | 0.000 | Benign | 4.10 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 2 | 0.0 | -0.98 | ||||||||||||||||||||||||||||||
| c.296A>C | E99A 2D AIThe SynGAP1 E99A missense change is not reported in ClinVar and has no entry in gnomAD. Consensus‑based predictors cluster around a benign interpretation: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all score the variant as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” verdict. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools therefore converge on a benign prediction: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta data are missing. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -3.173 | Likely Benign | 0.347 | Ambiguous | Likely Benign | 0.127 | Likely Benign | 0.4245 | 0.7548 | -1.49 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.07 | Benign | 0.00 | Affected | 0 | -1 | 5.3 | -58.04 | |||||||||||||||||||||||||||||||||||
| c.296A>G | E99G 2D AIThe SynGAP1 missense variant E99G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -3.031 | Likely Benign | 0.259 | Likely Benign | Likely Benign | 0.145 | Likely Benign | 0.3048 | 0.6399 | -1.69 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.04 | Benign | 0.00 | Affected | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||
| c.296A>T | E99V 2D AIThe SynGAP1 missense variant E99V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus likewise reports Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for E99V, 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 | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -3.628 | Likely Benign | 0.544 | Ambiguous | Likely Benign | 0.208 | Likely Benign | 0.1109 | 0.8175 | -1.69 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.02 | Benign | 0.00 | Affected | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||
| c.297A>C | E99D 2D AIThe SynGAP1 missense variant E99D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that E99D 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 | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -3.323 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.101 | Likely Benign | 0.2360 | 0.5200 | -0.78 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.09 | Benign | 0.00 | Affected | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.297A>T | E99D 2D AIThe SynGAP1 missense variant E99D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that E99D 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 | 0.795062 | Disordered | 0.645246 | Binding | 0.325 | 0.874 | 0.500 | -3.323 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.101 | Likely Benign | 0.2360 | 0.5200 | -0.78 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.09 | Benign | 0.00 | Affected | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.376T>A | F126I 2D  AIThe SynGAP1 missense variant F126I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify it as benign. Only two tools predict pathogenicity—SIFT and AlphaMissense‑Default. High‑accuracy consensus methods reinforce the benign assessment: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and AlphaMissense‑Optimized itself predicts benign. The protein‑folding stability predictor Foldetta was not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -2.919 | Likely Benign | 0.735 | Likely Pathogenic | Likely Benign | 0.044 | Likely Benign | 0.2569 | 0.2418 | -2.20 | Neutral | 0.160 | Benign | 0.045 | Benign | 3.95 | Benign | 0.00 | Affected | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.376T>C | F126L 2D  AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -0.992 | Likely Benign | 0.948 | Likely Pathogenic | Ambiguous | 0.091 | Likely Benign | 0.2780 | 0.3399 | -2.27 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.01 | Benign | 0.00 | Affected | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.376T>G | F126V 2D  AIThe SynGAP1 missense variant F126V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for F126V, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -1.584 | Likely Benign | 0.635 | Likely Pathogenic | Likely Benign | 0.086 | Likely Benign | 0.2496 | 0.2646 | -2.47 | Neutral | 0.160 | Benign | 0.045 | Benign | 3.98 | Benign | 0.00 | Affected | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||
| c.377T>A | F126Y 2D  AIThe SynGAP1 missense variant F126Y has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -3.519 | Likely Benign | 0.509 | Ambiguous | Likely Benign | 0.044 | Likely Benign | 0.1631 | 0.1907 | -1.29 | Neutral | 0.851 | Possibly Damaging | 0.221 | Benign | 3.90 | Benign | 0.00 | Affected | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.377T>C | F126S 2D  AIThe SynGAP1 missense variant F126S is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic effect. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” Overall, the majority of high‑accuracy tools (REVEL, PROVEAN, polyPhen‑2, ESM1b, FATHMM, and SGM‑Consensus) support a benign interpretation, while only two tools (SIFT, AlphaMissense‑Default) suggest pathogenicity. Given the preponderance of benign predictions and the absence of ClinVar evidence, the variant is most likely benign and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -0.234 | Likely Benign | 0.844 | Likely Pathogenic | Ambiguous | 0.086 | Likely Benign | 0.4833 | 0.0000 | -2.46 | Neutral | 0.160 | Benign | 0.045 | Benign | 3.96 | Benign | 0.00 | Affected | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||
| c.377T>G | F126C 2D  AIThe SynGAP1 missense variant F126C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (five) than benignity (three), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -2.553 | Likely Benign | 0.824 | Likely Pathogenic | Ambiguous | 0.109 | Likely Benign | 0.2682 | 0.1270 | -3.19 | Deleterious | 0.952 | Possibly Damaging | 0.570 | Possibly Damaging | 3.88 | Benign | 0.00 | Affected | -4 | -2 | -0.3 | -44.04 | ||||||||||||||||||||||||||||||||||||
| c.378C>A | F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -0.992 | Likely Benign | 0.948 | Likely Pathogenic | Ambiguous | 0.114 | Likely Benign | 0.2780 | 0.3399 | -2.27 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.01 | Benign | 0.00 | Affected | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.378C>G | F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact; the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.712056 | Binding | 0.316 | 0.874 | 0.500 | -0.992 | Likely Benign | 0.948 | Likely Pathogenic | Ambiguous | 0.114 | Likely Benign | 0.2780 | 0.3399 | -2.27 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.01 | Benign | 0.00 | Affected | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.2629C>A | L877M 2D AIThe SynGAP1 missense variant L877M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the two polyPhen‑2 scores (HumDiv and HumVar) predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.653063 | Disordered | 0.634010 | Binding | 0.265 | 0.875 | 0.250 | -6.266 | Likely Benign | 0.134 | Likely Benign | Likely Benign | 0.068 | Likely Benign | 0.0813 | 0.3532 | -0.55 | Neutral | 0.922 | Possibly Damaging | 0.776 | Possibly Damaging | 2.58 | Benign | 0.15 | Tolerated | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||
| c.2629C>G | L877V 2D AIThe SynGAP1 missense variant L877V is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.653063 | Disordered | 0.634010 | Binding | 0.265 | 0.875 | 0.250 | -5.063 | Likely Benign | 0.097 | Likely Benign | Likely Benign | 0.022 | Likely Benign | 0.1726 | 0.3178 | -0.10 | Neutral | 0.232 | Benign | 0.109 | Benign | 2.71 | Benign | 0.26 | Tolerated | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2630T>A | L877Q 2D  AIThe SynGAP1 missense variant L877Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The 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 (which integrates FoldX‑MD and Rosetta outputs) is not available 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 | 0.653063 | Disordered | 0.634010 | Binding | 0.265 | 0.875 | 0.250 | -5.919 | Likely Benign | 0.460 | Ambiguous | Likely Benign | 0.152 | Likely Benign | 0.1208 | 0.0919 | -1.58 | Neutral | 0.986 | Probably Damaging | 0.876 | Possibly Damaging | 2.57 | Benign | 0.03 | Affected | -2 | -2 | -7.3 | 14.97 | |||||||||||||||||||||||||||||||||||
| c.2630T>C | L877P 2D  AIThe SynGAP1 missense variant L877P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.653063 | Disordered | 0.634010 | Binding | 0.265 | 0.875 | 0.250 | -4.960 | Likely Benign | 0.312 | Likely Benign | Likely Benign | 0.154 | Likely Benign | 0.3899 | 0.1543 | -1.57 | Neutral | 0.986 | Probably Damaging | 0.876 | Possibly Damaging | 2.59 | Benign | 0.03 | Affected | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||
| c.2630T>G | L877R 2D  AIThe SynGAP1 missense variant L877R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.653063 | Disordered | 0.634010 | Binding | 0.265 | 0.875 | 0.250 | -6.678 | Likely Benign | 0.673 | Likely Pathogenic | Likely Benign | 0.148 | Likely Benign | 0.1218 | 0.0761 | -1.82 | Neutral | 0.986 | Probably Damaging | 0.876 | Possibly Damaging | 2.57 | Benign | 0.02 | Affected | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||
| c.271G>A | E91K 2D AISynGAP1 E91K is not reported in ClinVar and is absent from gnomAD. Computational predictors fall into two groups: benign calls (REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus “Likely Benign”) and pathogenic calls (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy tools give conflicting results: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts benign; Foldetta data are unavailable. Consequently, the evidence is split, but the consensus of the most reliable predictors leans toward a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | -4.964 | Likely Benign | 0.962 | Likely Pathogenic | Likely Pathogenic | 0.146 | Likely Benign | 0.2693 | 0.7444 | -1.07 | Neutral | 0.880 | Possibly Damaging | 0.636 | Possibly Damaging | 3.92 | Benign | 0.00 | Affected | 0 | 1 | -0.4 | -0.94 | |||||||||||||||||||||||||||||||||||
| c.271G>C | E91Q 2D AIThe SynGAP1 missense variant E91Q has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Overall, the predictions are mixed, with an equal number of benign and pathogenic calls, but the consensus‑based SGM‑Consensus and the majority of individual benign predictions lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | -4.053 | Likely Benign | 0.805 | Likely Pathogenic | Ambiguous | 0.103 | Likely Benign | 0.1487 | 0.7442 | -0.89 | Neutral | 0.947 | Possibly Damaging | 0.727 | Possibly Damaging | 3.89 | Benign | 0.00 | Affected | 2 | 2 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||
| c.272A>C | E91A 2D AIThe SynGAP1 missense variant E91A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. Overall, the majority of consensus‑based and individual predictors lean toward a benign classification, with several high‑confidence tools indicating pathogenicity, leaving the assessment inconclusive. Based on the available predictions, the variant is most likely benign, and this does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | -3.302 | Likely Benign | 0.815 | Likely Pathogenic | Ambiguous | 0.094 | Likely Benign | 0.4511 | 0.7077 | -1.58 | Neutral | 0.880 | Possibly Damaging | 0.636 | Possibly Damaging | 3.89 | Benign | 0.00 | Affected | 0 | -1 | 5.3 | -58.04 | |||||||||||||||||||||||||||||||||||
| c.272A>G | E91G 2D AIThe SynGAP1 missense variant E91G is listed in ClinVar (ID 436922.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicating a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar designation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | Likely Benign | 1 | -3.226 | Likely Benign | 0.783 | Likely Pathogenic | Likely Benign | 0.110 | Likely Benign | 0.3418 | 0.6030 | -2.18 | Neutral | 0.947 | Possibly Damaging | 0.727 | Possibly Damaging | 3.86 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||
| c.272A>T | E91V 2D AIThe SynGAP1 E91V missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Overall, the evidence is mixed, but the consensus of several independent benign predictors and the SGM‑Consensus lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | -3.697 | Likely Benign | 0.934 | Likely Pathogenic | Ambiguous | 0.124 | Likely Benign | 0.0940 | 0.7457 | -2.16 | Neutral | 0.947 | Possibly Damaging | 0.788 | Possibly Damaging | 3.84 | Benign | 0.00 | Affected | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||
| c.273G>C | E91D 2D AIThe SynGAP1 missense variant E91D is reported in gnomAD (variant ID 6‑33425881‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | 6-33425881-G-C | 1 | 6.20e-7 | -3.160 | Likely Benign | 0.293 | Likely Benign | Likely Benign | 0.095 | Likely Benign | 0.2000 | 0.5219 | -0.84 | Neutral | 0.880 | Possibly Damaging | 0.636 | Possibly Damaging | 3.98 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 3 | 0.0 | -14.03 | ||||||||||||||||||||||||||||||
| c.273G>T | E91D 2D AIThe SynGAP1 missense variant E91D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.575842 | Disordered | 0.533667 | Binding | 0.303 | 0.875 | 0.500 | -3.160 | Likely Benign | 0.293 | Likely Benign | Likely Benign | 0.095 | Likely Benign | 0.2000 | 0.5219 | -0.84 | Neutral | 0.880 | Possibly Damaging | 0.636 | Possibly Damaging | 3.98 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 3 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||
| c.283C>A | H95N 2D  AIThe SynGAP1 missense variant H95N 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 only pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence overwhelmingly supports a benign classification for H95N, 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 | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | -3.454 | Likely Benign | 0.069 | Likely Benign | Likely Benign | 0.089 | Likely Benign | 0.1821 | 0.2491 | -1.12 | Neutral | 0.219 | Benign | 0.009 | Benign | 4.20 | Benign | 0.00 | Affected | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||
| c.283C>G | H95D 2D  AIThe SynGAP1 missense variant H95D is not listed in ClinVar and is present in gnomAD (variant ID 6‑33425891‑C‑G). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus also reports 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 supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | 6-33425891-C-G | 3 | 1.86e-6 | -2.387 | Likely Benign | 0.188 | Likely Benign | Likely Benign | 0.092 | Likely Benign | 0.2759 | 0.1801 | -0.81 | Neutral | 0.084 | Benign | 0.009 | Benign | 4.22 | Benign | 0.00 | Affected | 4.32 | 1 | -1 | 1 | -0.3 | -22.05 | ||||||||||||||||||||||||||||||
| c.283C>T | H95Y 2D  AIThe SynGAP1 missense variant H95Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence indicates that H95Y 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 | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | -3.610 | Likely Benign | 0.112 | Likely Benign | Likely Benign | 0.090 | Likely Benign | 0.0880 | 0.4122 | -1.45 | Neutral | 0.219 | Benign | 0.014 | Benign | 4.14 | Benign | 0.00 | Affected | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||
| c.284A>C | H95P 2D  AIThe SynGAP1 missense variant H95P 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 the single pathogenic call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence indicates that H95P is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | -1.611 | Likely Benign | 0.045 | Likely Benign | Likely Benign | 0.164 | Likely Benign | 0.2244 | 0.3704 | -1.66 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.19 | Benign | 0.00 | Affected | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||
| c.284A>G | H95R 2D  AIThe SynGAP1 missense variant H95R is reported in gnomAD (variant ID 6‑33425892‑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, while only SIFT predicts it as pathogenic. 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 likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H95R is most likely benign, and this conclusion does not contradict any ClinVar status (none is provided). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | 6-33425892-A-G | 1 | 6.20e-7 | -2.789 | Likely Benign | 0.153 | Likely Benign | Likely Benign | 0.043 | Likely Benign | 0.1907 | 0.2087 | -1.31 | Neutral | 0.084 | Benign | 0.009 | Benign | 4.20 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||
| c.284A>T | H95L 2D  AIThe SynGAP1 missense variant H95L is not reported 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 results are not available for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | -1.967 | Likely Benign | 0.073 | Likely Benign | Likely Benign | 0.085 | Likely Benign | 0.1017 | 0.5074 | -2.31 | Neutral | 0.084 | Benign | 0.007 | Benign | 4.17 | Benign | 0.00 | Affected | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||
| c.285C>A | H95Q 2D  AIThe SynGAP1 missense variant H95Q is reported in gnomAD (ID 6‑33425893‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments 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 overall assessment. Overall, the preponderance of predictions indicates that H95Q 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 | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | 6-33425893-C-A | 1 | 6.20e-7 | -3.355 | Likely Benign | 0.084 | Likely Benign | Likely Benign | 0.070 | Likely Benign | 0.1551 | 0.3375 | -0.97 | Neutral | 0.633 | Possibly Damaging | 0.017 | Benign | 4.21 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 3 | -0.3 | -9.01 | ||||||||||||||||||||||||||||||
| c.285C>G | H95Q 2D AIThe SynGAP1 missense variant H95Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenicity, but these two tools are in minority. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores 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 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 | 0.661982 | Disordered | 0.590542 | Binding | 0.335 | 0.875 | 0.625 | -3.355 | Likely Benign | 0.084 | Likely Benign | Likely Benign | 0.070 | Likely Benign | 0.1551 | 0.3375 | -0.97 | Neutral | 0.633 | Possibly Damaging | 0.017 | Benign | 4.21 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 3 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||
| c.235A>C | N79H 2D  AIThe SynGAP1 missense variant N79H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -2.090 | Likely Benign | 0.110 | Likely Benign | Likely Benign | 0.045 | Likely Benign | 0.1247 | 0.4718 | -0.72 | Neutral | 0.939 | Possibly Damaging | 0.114 | Benign | 4.16 | Benign | 0.00 | Affected | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||
| c.235A>G | N79D 2D  AIThe SynGAP1 missense variant N79D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -3.746 | Likely Benign | 0.281 | Likely Benign | Likely Benign | 0.021 | Likely Benign | 0.1893 | 0.2535 | -0.92 | Neutral | 0.371 | Benign | 0.018 | Benign | 4.19 | Benign | 0.00 | Affected | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.235A>T | N79Y 2D  AIThe SynGAP1 missense variant N79Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -2.844 | Likely Benign | 0.250 | Likely Benign | Likely Benign | 0.039 | Likely Benign | 0.0510 | 0.4389 | -1.35 | Neutral | 0.939 | Possibly Damaging | 0.114 | Benign | 4.13 | Benign | 0.00 | Affected | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||
| c.236A>C | N79T 2D  AIThe SynGAP1 missense variant N79T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -3.752 | Likely Benign | 0.102 | Likely Benign | Likely Benign | 0.022 | Likely Benign | 0.1133 | 0.4890 | -0.61 | Neutral | 0.371 | Benign | 0.018 | Benign | 4.21 | Benign | 0.00 | Affected | 0 | 0 | 2.8 | -13.00 | |||||||||||||||||||||||||||||||||||
| c.236A>G | N79S 2D  AIThe SynGAP1 missense variant N79S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -2.311 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.017 | Likely Benign | 0.3155 | 0.4740 | -0.31 | Neutral | 0.113 | Benign | 0.011 | Benign | 4.29 | Benign | 0.00 | Affected | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||
| c.236A>T | N79I 2D  AIThe SynGAP1 missense variant N79I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | -3.958 | Likely Benign | 0.337 | Likely Benign | Likely Benign | 0.030 | Likely Benign | 0.0572 | 0.4924 | -1.42 | Neutral | 0.939 | Possibly Damaging | 0.080 | Benign | 4.14 | Benign | 0.00 | Affected | -2 | -3 | 8.0 | -0.94 | |||||||||||||||||||||||||||||||||||
| c.237C>A | N79K 2D  AIThe SynGAP1 missense variant N79K is listed in gnomAD (ID 6‑33425845‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores benign and the SGM‑Consensus indicates “Likely Benign.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | 6-33425845-C-A | 1 | 6.20e-7 | -2.811 | Likely Benign | 0.422 | Ambiguous | Likely Benign | 0.030 | Likely Benign | 0.1883 | 0.3929 | -0.91 | Neutral | 0.001 | Benign | 0.000 | Benign | 4.22 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 1 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||
| c.237C>G | N79K 2D AIThe SynGAP1 missense variant N79K is listed in gnomAD (ID 6‑33425845‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. 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 | 0.618285 | Disordered | 0.457064 | Uncertain | 0.290 | 0.876 | 0.375 | 6-33425845-C-G | 1 | 6.20e-7 | -2.811 | Likely Benign | 0.422 | Ambiguous | Likely Benign | 0.030 | Likely Benign | 0.1883 | 0.3929 | -0.91 | Neutral | 0.001 | Benign | 0.000 | Benign | 4.22 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 1 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||
| c.2254T>A | S752T 2D AIThe SynGAP1 missense variant S752T is not reported 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM 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, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.690594 | Binding | 0.365 | 0.877 | 0.625 | -4.040 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.029 | Likely Benign | 0.1633 | 0.6342 | -1.33 | Neutral | 0.248 | Benign | 0.137 | Benign | 1.55 | Pathogenic | 0.07 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2254T>C | S752P 2D AIThe SynGAP1 missense variant S752P 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, 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 stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for S752P, and this conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.690594 | Binding | 0.365 | 0.877 | 0.625 | -3.491 | Likely Benign | 0.158 | Likely Benign | Likely Benign | 0.183 | Likely Benign | 0.2288 | 0.5882 | -1.09 | Neutral | 0.998 | Probably Damaging | 0.912 | Probably Damaging | 1.51 | Pathogenic | 0.02 | Affected | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||
| c.2254T>G | S752A 2D AIThe SynGAP1 missense variant S752A has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are 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 | 0.604312 | Disordered | 0.690594 | Binding | 0.365 | 0.877 | 0.625 | -3.258 | Likely Benign | 0.092 | Likely Benign | Likely Benign | 0.074 | Likely Benign | 0.5092 | 0.5634 | Strenghten | -1.42 | Neutral | 0.910 | Possibly Damaging | 0.524 | Possibly Damaging | 1.59 | Pathogenic | 0.04 | Affected | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||
| c.2255C>G | S752W 2D  AIThe SynGAP1 missense variant S752W is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion is not contradicted by ClinVar status (which is absent). Thus, the variant is most likely pathogenic based on the collective evidence, despite the single benign prediction from AlphaMissense‑Optimized. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.690594 | Binding | 0.365 | 0.877 | 0.625 | -6.771 | Likely Benign | 0.565 | Likely Pathogenic | Likely Benign | 0.341 | Likely Benign | 0.0837 | 0.6241 | -3.54 | Deleterious | 1.000 | Probably Damaging | 0.992 | Probably Damaging | 1.49 | Pathogenic | 0.00 | Affected | -2 | -3 | -0.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.2255C>T | S752L 2D  AIThe SynGAP1 missense variant S752L is listed in ClinVar with an “Uncertain” status (ClinVar ID 2143952.0) and is present in gnomAD (ID 6‑33441720‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.690594 | Binding | 0.365 | 0.877 | 0.625 | Uncertain | 2 | 6-33441720-C-T | 6 | 3.72e-6 | -3.386 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.195 | Likely Benign | 0.1308 | 0.5909 | -2.09 | Neutral | 0.993 | Probably Damaging | 0.641 | Possibly Damaging | 1.51 | Pathogenic | 0.01 | Affected | 3.99 | 5 | -3 | -2 | 4.6 | 26.08 | ||||||||||||||||||||||||||||
| c.2302G>A | D768N 2D  AIThe SynGAP1 missense variant D768N is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442460‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus is “Likely Benign,” and Foldetta data are unavailable. Overall, the consensus of available predictions indicates that the variant is most likely benign, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | Uncertain | 1 | 6-33442460-G-A | 2 | 2.57e-6 | -6.892 | Likely Benign | 0.453 | Ambiguous | Likely Benign | 0.048 | Likely Benign | 0.1178 | 0.7843 | -0.77 | Neutral | 0.106 | Benign | 0.009 | Benign | 4.07 | Benign | 0.96 | Tolerated | 3.64 | 6 | 1 | 2 | 0.0 | -0.98 | ||||||||||||||||||||||||||||
| c.2302G>C | D768H 2D  AIThe SynGAP1 D768H missense variant is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of predictions (5 benign vs. 4 pathogenic) and the high‑accuracy benign call suggest the variant is most likely benign, with no ClinVar status to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | -8.673 | Likely Pathogenic | 0.783 | Likely Pathogenic | Likely Benign | 0.160 | Likely Benign | 0.1450 | 0.8136 | -1.85 | Neutral | 0.966 | Probably Damaging | 0.737 | Possibly Damaging | 4.03 | Benign | 0.12 | Tolerated | 1 | -1 | 0.3 | 22.05 | ||||||||||||||||||||||||||||||||||||
| c.2302G>T | D768Y 2D  AIThe SynGAP1 missense variant D768Y is listed in ClinVar with status “Uncertain” (ClinVar ID 1061652.0) and is present in gnomAD (variant ID 6‑33442460‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar designation of uncertainty. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | Uncertain | 1 | 6-33442460-G-T | -9.866 | Likely Pathogenic | 0.824 | Likely Pathogenic | Ambiguous | 0.234 | Likely Benign | 0.0581 | 0.7525 | -2.86 | Deleterious | 0.989 | Probably Damaging | 0.806 | Possibly Damaging | 4.01 | Benign | 0.07 | Tolerated | 3.64 | 6 | -4 | -3 | 2.2 | 48.09 | ||||||||||||||||||||||||||||||
| c.2303A>C | D768A 2D  AIThe SynGAP1 D768A variant is listed in gnomAD (ID 6‑33442461‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic predictions (ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and thus unavailable; Foldetta stability analysis is not reported. Overall, the preponderance of evidence (six benign vs two pathogenic) points to a benign effect. This conclusion does not contradict ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | 6-33442461-A-C | -8.153 | Likely Pathogenic | 0.786 | Likely Pathogenic | Ambiguous | 0.174 | Likely Benign | 0.3924 | 0.7662 | -1.84 | Neutral | 0.245 | Benign | 0.096 | Benign | 4.09 | Benign | 0.14 | Tolerated | 3.64 | 6 | -2 | 0 | 5.3 | -44.01 | |||||||||||||||||||||||||||||||||
| c.2303A>G | D768G 2D  AIThe SynGAP1 D768G missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all predict benign, whereas AlphaMissense‑Default predicts pathogenic. The high‑accuracy AlphaMissense‑Optimized result is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, which would provide a protein‑folding stability assessment, has no available output for this variant. Overall, the preponderance of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | -7.150 | In-Between | 0.697 | Likely Pathogenic | Likely Benign | 0.184 | Likely Benign | 0.4130 | 0.7476 | 0.03 | Neutral | 0.393 | Benign | 0.131 | Benign | 4.09 | Benign | 0.72 | Tolerated | 1 | -1 | 3.1 | -58.04 | ||||||||||||||||||||||||||||||||||||
| c.2303A>T | D768V 2D  AIThe SynGAP1 D768V variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | -9.528 | Likely Pathogenic | 0.880 | Likely Pathogenic | Ambiguous | 0.164 | Likely Benign | 0.0802 | 0.8019 | -2.62 | Deleterious | 0.611 | Possibly Damaging | 0.140 | Benign | 4.04 | Benign | 0.02 | Affected | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||
| c.2304C>A | D768E 2D  AIThe SynGAP1 missense variant D768E is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts a benign outcome. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the computational evidence strongly supports a benign effect for D768E, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | -4.611 | Likely Benign | 0.380 | Ambiguous | Likely Benign | 0.065 | Likely Benign | 0.1368 | 0.7729 | -1.23 | Neutral | 0.393 | Benign | 0.171 | Benign | 4.16 | Benign | 0.17 | Tolerated | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2304C>G | D768E 2D AIThe SynGAP1 missense variant D768E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence strongly suggests that D768E is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.332115 | Structured | 0.928237 | Binding | 0.314 | 0.877 | 0.250 | -4.611 | Likely Benign | 0.380 | Ambiguous | Likely Benign | 0.065 | Likely Benign | 0.1368 | 0.7729 | -1.23 | Neutral | 0.393 | Benign | 0.171 | Benign | 4.16 | Benign | 0.17 | Tolerated | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2494C>A | Q832K 2D AIThe SynGAP1 missense variant Q832K 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 variant 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 further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that 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 | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -4.964 | Likely Benign | 0.182 | Likely Benign | Likely Benign | 0.080 | Likely Benign | 0.1759 | 0.3568 | -0.87 | Neutral | 0.811 | Possibly Damaging | 0.348 | Benign | 2.78 | Benign | 0.10 | Tolerated | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.2494C>G | Q832E 2D AIThe SynGAP1 missense variant Q832E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -3.024 | Likely Benign | 0.098 | Likely Benign | Likely Benign | 0.109 | Likely Benign | 0.1262 | 0.1897 | -0.37 | Neutral | 0.652 | Possibly Damaging | 0.311 | Benign | 2.77 | Benign | 0.06 | Tolerated | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.2495A>C | Q832P 2D AIThe SynGAP1 missense variant Q832P is not reported 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 | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -1.882 | Likely Benign | 0.066 | Likely Benign | Likely Benign | 0.142 | Likely Benign | 0.1959 | 0.4368 | -1.07 | Neutral | 0.002 | Benign | 0.005 | Benign | 2.70 | Benign | 0.05 | Affected | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.2495A>G | Q832R 2D AIThe SynGAP1 missense variant Q832R 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 further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -3.680 | Likely Benign | 0.203 | Likely Benign | Likely Benign | 0.087 | Likely Benign | 0.1494 | 0.1434 | -1.17 | Neutral | 0.912 | Possibly Damaging | 0.424 | Benign | 2.74 | Benign | 0.09 | Tolerated | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.2495A>T | Q832L 2D AIThe SynGAP1 missense variant Q832L 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 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 interpretation: 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 does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -2.299 | Likely Benign | 0.190 | Likely Benign | Likely Benign | 0.090 | Likely Benign | 0.0676 | 0.4852 | -0.58 | Neutral | 0.811 | Possibly Damaging | 0.424 | Benign | 2.84 | Benign | 1.00 | Tolerated | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.2496G>C | Q832H 2D AIThe SynGAP1 missense variant Q832H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, 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 consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -3.322 | Likely Benign | 0.197 | Likely Benign | Likely Benign | 0.071 | Likely Benign | 0.1263 | 0.3230 | -1.24 | Neutral | 0.064 | Benign | 0.038 | Benign | 2.76 | Benign | 0.03 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.2496G>T | Q832H 2D AIThe SynGAP1 missense variant Q832H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, 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 consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.720929 | Disordered | 0.619913 | Binding | 0.290 | 0.877 | 0.375 | -3.322 | Likely Benign | 0.197 | Likely Benign | Likely Benign | 0.071 | Likely Benign | 0.1263 | 0.3230 | -1.24 | Neutral | 0.064 | Benign | 0.038 | Benign | 2.76 | Benign | 0.03 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.307G>A | G103S 2D  AIThe SynGAP1 missense variant G103S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -3.177 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.072 | Likely Benign | 0.2816 | 0.4867 | -0.03 | Neutral | 0.565 | Possibly Damaging | 0.207 | Benign | 4.32 | Benign | 0.00 | Affected | 1 | 0 | -0.4 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.307G>C | G103R 2D AIThe SynGAP1 missense variant G103R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -3.384 | Likely Benign | 0.710 | Likely Pathogenic | Likely Benign | 0.100 | Likely Benign | 0.1198 | 0.4362 | 0.00 | Neutral | 0.949 | Possibly Damaging | 0.708 | Possibly Damaging | 4.27 | Benign | 0.00 | Affected | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.307G>T | G103C 2D  AIThe SynGAP1 missense variant G103C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect for G103C, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -5.681 | Likely Benign | 0.136 | Likely Benign | Likely Benign | 0.128 | Likely Benign | 0.1494 | 0.3767 | -1.12 | Neutral | 0.995 | Probably Damaging | 0.829 | Possibly Damaging | 4.17 | Benign | 0.00 | Affected | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||
| c.308G>A | G103D 2D  AIThe SynGAP1 missense variant G103D is not reported in ClinVar and has no entry in gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight benign predictions: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the balance of evidence points to a benign effect for G103D, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -3.523 | Likely Benign | 0.477 | Ambiguous | Likely Benign | 0.110 | Likely Benign | 0.2237 | 0.2896 | -0.10 | Neutral | 0.949 | Possibly Damaging | 0.617 | Possibly Damaging | 4.26 | Benign | 0.00 | Affected | 1 | -1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||
| c.308G>C | G103A 2D AIThe SynGAP1 missense variant G103A 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 reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign outcome. Foldetta results are not available, so they do not influence the assessment. Overall, the majority 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 | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -3.549 | Likely Benign | 0.092 | Likely Benign | Likely Benign | 0.118 | Likely Benign | 0.3941 | 0.3784 | -0.08 | Neutral | 0.008 | Benign | 0.008 | Benign | 4.31 | Benign | 0.00 | Affected | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.308G>T | G103V 2D AIThe SynGAP1 missense variant G103V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.687376 | Binding | 0.381 | 0.877 | 0.625 | -3.584 | Likely Benign | 0.151 | Likely Benign | Likely Benign | 0.126 | Likely Benign | 0.1420 | 0.3404 | -0.96 | Neutral | 0.820 | Possibly Damaging | 0.376 | Benign | 4.22 | Benign | 0.00 | Affected | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1874 | 0.6902 | -0.57 | Neutral | 0.790 | Possibly Damaging | 0.433 | Benign | 2.59 | Benign | 0.16 | Tolerated | 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 | 0.2322 | 0.6099 | -1.31 | Neutral | 0.990 | Probably Damaging | 0.798 | Possibly Damaging | 2.46 | Pathogenic | 0.13 | Tolerated | 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 | 0.4692 | 0.5403 | -0.78 | Neutral | 0.447 | Benign | 0.252 | Benign | 2.66 | Benign | 1.00 | Tolerated | 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 | 0.1007 | 0.5877 | -2.07 | Neutral | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 2.45 | Pathogenic | 0.02 | Affected | 3.77 | 5 | -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 | 0.1403 | 0.6309 | -1.81 | Neutral | 0.997 | Probably Damaging | 0.946 | Probably Damaging | 2.45 | Pathogenic | 0.05 | Affected | 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 | 0.0925 | 0.5851 | -2.17 | Neutral | 0.990 | Probably Damaging | 0.856 | Possibly Damaging | 2.45 | Pathogenic | 0.02 | Affected | -3 | -2 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||
| c.349A>C | S117R 2D  AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -4.187 | Likely Benign | 0.971 | Likely Pathogenic | Likely Pathogenic | 0.276 | Likely Benign | 0.1040 | 0.3770 | -1.81 | Neutral | 0.845 | Possibly Damaging | 0.326 | Benign | 3.70 | Benign | 0.01 | Affected | 3.61 | 5 | -1 | 0 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||
| c.349A>G | S117G 2D  AIThe SynGAP1 missense variant S117G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -3.280 | Likely Benign | 0.174 | Likely Benign | Likely Benign | 0.122 | Likely Benign | 0.2113 | 0.4627 | -1.59 | Neutral | 0.390 | Benign | 0.066 | Benign | 3.73 | Benign | 0.01 | Affected | 1 | 0 | 0.4 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.349A>T | S117C 2D AIThe SynGAP1 missense variant S117C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -5.980 | Likely Benign | 0.201 | Likely Benign | Likely Benign | 0.246 | Likely Benign | 0.1222 | 0.5057 | -1.81 | Neutral | 0.992 | Probably Damaging | 0.667 | Possibly Damaging | 3.68 | Benign | 0.00 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.350G>A | S117N 2D  AIThe SynGAP1 missense variant S117N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and consensus analyses indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -5.704 | Likely Benign | 0.489 | Ambiguous | Likely Benign | 0.067 | Likely Benign | 0.1491 | 0.4530 | -1.06 | Neutral | 0.005 | Benign | 0.003 | Benign | 3.71 | Benign | 0.01 | Affected | 1 | 1 | -2.7 | 27.03 | |||||||||||||||||||||||||||||||||||
| c.350G>C | S117T 2D AIThe SynGAP1 missense variant S117T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -4.602 | Likely Benign | 0.142 | Likely Benign | Likely Benign | 0.089 | Likely Benign | 0.1527 | 0.5505 | -0.98 | Neutral | 0.608 | Possibly Damaging | 0.092 | Benign | 3.79 | Benign | 0.02 | Affected | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.350G>T | S117I 2D  AIThe SynGAP1 missense variant S117I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -5.483 | Likely Benign | 0.559 | Ambiguous | Likely Benign | 0.137 | Likely Benign | 0.1060 | 0.5048 | -2.33 | Neutral | 0.971 | Probably Damaging | 0.598 | Possibly Damaging | 3.70 | Benign | 0.00 | Affected | -1 | -2 | 5.3 | 26.08 | |||||||||||||||||||||||||||||||||||
| c.351C>A | S117R 2D AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) and the consensus evidence lean toward a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | -4.187 | Likely Benign | 0.971 | Likely Pathogenic | Likely Pathogenic | 0.144 | Likely Benign | 0.1040 | 0.3770 | -1.81 | Neutral | 0.845 | Possibly Damaging | 0.326 | Benign | 3.70 | Benign | 0.01 | Affected | 3.61 | 5 | -1 | 0 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||
| c.351C>G | S117R 2D AIThe SynGAP1 missense variant S117R is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33432216‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a pathogenic ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.672422 | Binding | 0.357 | 0.877 | 0.625 | 6-33432216-C-G | 1 | 6.20e-7 | -4.187 | Likely Benign | 0.971 | Likely Pathogenic | Likely Pathogenic | 0.144 | Likely Benign | 0.1040 | 0.3770 | -1.81 | Neutral | 0.845 | Possibly Damaging | 0.326 | Benign | 3.70 | Benign | 0.01 | Affected | 3.61 | 5 | -1 | 0 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||
| c.421A>C | I141L 2D  AIThe SynGAP1 missense variant I141L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -6.563 | Likely Benign | 0.787 | Likely Pathogenic | Ambiguous | 0.156 | Likely Benign | 0.0742 | 0.3180 | -1.00 | Neutral | 0.016 | Benign | 0.013 | Benign | 3.84 | Benign | 0.10 | Tolerated | 2 | 2 | -0.7 | 0.00 | |||||||||||||||||||||||||||||||||||
| c.421A>G | I141V 2D  AIThe SynGAP1 I141V missense variant is catalogued in gnomAD (ID 6‑33432718‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM) and pathogenic (SIFT, AlphaMissense‑Default). The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the preponderance of evidence points to a benign effect, and this assessment aligns with the lack of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | 6-33432718-A-G | 1 | 6.42e-7 | -4.030 | Likely Benign | 0.785 | Likely Pathogenic | Ambiguous | 0.125 | Likely Benign | 0.1101 | 0.3464 | -0.58 | Neutral | 0.016 | Benign | 0.021 | Benign | 3.74 | Benign | 0.03 | Affected | 3.61 | 5 | 3 | 4 | -0.3 | -14.03 | ||||||||||||||||||||||||||||||
| c.421A>T | I141F 2D  AIThe SynGAP1 missense variant I141F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -9.621 | Likely Pathogenic | 0.980 | Likely Pathogenic | Likely Pathogenic | 0.221 | Likely Benign | 0.0489 | 0.2775 | -1.82 | Neutral | 0.001 | Benign | 0.002 | Benign | 3.57 | Benign | 0.01 | Affected | 1 | 0 | -1.7 | 34.02 | ||||||||||||||||||||||||||||||||||||
| c.422T>A | I141N 2D  AIThe SynGAP1 missense variant I141N is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic. Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141N. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -12.417 | Likely Pathogenic | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.258 | Likely Benign | 0.1047 | 0.0270 | -3.90 | Deleterious | 0.799 | Possibly Damaging | 0.424 | Benign | 3.54 | Benign | 0.00 | Affected | -2 | -3 | -8.0 | 0.94 | |||||||||||||||||||||||||||||||||||
| c.422T>C | I141T 2D  AIThe SynGAP1 missense variant I141T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its contribution is unavailable. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -10.580 | Likely Pathogenic | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.251 | Likely Benign | 0.1165 | 0.1214 | -2.81 | Deleterious | 0.272 | Benign | 0.167 | Benign | 3.57 | Benign | 0.00 | Affected | 0 | -1 | -5.2 | -12.05 | |||||||||||||||||||||||||||||||||||
| c.422T>G | I141S 2D  AIThe SynGAP1 missense variant I141S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus also as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -11.874 | Likely Pathogenic | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.267 | Likely Benign | 0.2885 | 0.0840 | -3.28 | Deleterious | 0.567 | Possibly Damaging | 0.249 | Benign | 3.56 | Benign | 0.00 | Affected | -1 | -2 | -5.3 | -26.08 | |||||||||||||||||||||||||||||||||||
| c.423C>G | I141M 2D  AIThe SynGAP1 I141M variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are mixed, with an equal split between benign and pathogenic calls and no definitive evidence from Foldetta. Thus, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.465241 | Structured | 0.577021 | Binding | 0.367 | 0.877 | 0.500 | -7.437 | In-Between | 0.962 | Likely Pathogenic | Likely Pathogenic | 0.112 | Likely Benign | 0.0664 | 0.2661 | -1.54 | Neutral | 0.567 | Possibly Damaging | 0.332 | Benign | 3.57 | Benign | 0.01 | Affected | 2 | 1 | -2.6 | 18.03 | ||||||||||||||||||||||||||||||||||||
| c.241C>A | L81M 2D AIThe SynGAP1 missense variant L81M is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33425849‑C‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.632174 | Disordered | 0.502033 | Binding | 0.291 | 0.878 | 0.250 | 6-33425849-C-A | 1 | 6.20e-7 | -5.351 | Likely Benign | 0.254 | Likely Benign | Likely Benign | 0.039 | Likely Benign | 0.0692 | 0.2432 | -0.27 | Neutral | 0.789 | Possibly Damaging | 0.165 | Benign | 3.95 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 4 | -1.9 | 18.03 | ||||||||||||||||||||||||||||||
| c.241C>G | L81V 2D AIThe SynGAP1 missense variant L81V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for L81V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.632174 | Disordered | 0.502033 | Binding | 0.291 | 0.878 | 0.250 | -5.207 | Likely Benign | 0.289 | Likely Benign | Likely Benign | 0.038 | Likely Benign | 0.1423 | 0.2653 | -0.51 | Neutral | 0.178 | Benign | 0.014 | Benign | 4.04 | Benign | 0.00 | Affected | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.242T>A | L81Q 2D AIThe SynGAP1 missense variant L81Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.632174 | Disordered | 0.502033 | Binding | 0.291 | 0.878 | 0.250 | -5.055 | Likely Benign | 0.517 | Ambiguous | Likely Benign | 0.052 | Likely Benign | 0.1046 | 0.0888 | -1.22 | Neutral | 0.919 | Possibly Damaging | 0.226 | Benign | 3.93 | Benign | 0.00 | Affected | -2 | -2 | -7.3 | 14.97 | |||||||||||||||||||||||||||||||||||
| c.242T>C | L81P 2D AIThe SynGAP1 missense variant L81P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.632174 | Disordered | 0.502033 | Binding | 0.291 | 0.878 | 0.250 | -4.413 | Likely Benign | 0.827 | Likely Pathogenic | Ambiguous | 0.095 | Likely Benign | 0.3062 | 0.1818 | -1.51 | Neutral | 0.919 | Possibly Damaging | 0.226 | Benign | 3.92 | Benign | 0.00 | Affected | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||
| c.242T>G | L81R 2D AIThe SynGAP1 missense variant L81R is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors shows a split: benign calls from REVEL, PROVEAN, polyPhen2_HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen2_HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability assessment is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.632174 | Disordered | 0.502033 | Binding | 0.291 | 0.878 | 0.250 | -4.451 | Likely Benign | 0.639 | Likely Pathogenic | Likely Benign | 0.053 | Likely Benign | 0.1179 | 0.0688 | -1.22 | Neutral | 0.919 | Possibly Damaging | 0.226 | Benign | 3.94 | Benign | 0.00 | Affected | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||
| c.259T>A | S87T 2D AIThe SynGAP1 missense variant S87T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote) also indicates benign. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -6.706 | Likely Benign | 0.776 | Likely Pathogenic | Likely Benign | 0.032 | Likely Benign | 0.1001 | 0.4708 | -1.23 | Neutral | 0.140 | Benign | 0.153 | Benign | 3.80 | Benign | 0.00 | Affected | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.259T>C | S87P 2D AIThe SynGAP1 missense variant S87P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -8.566 | Likely Pathogenic | 0.985 | Likely Pathogenic | Likely Pathogenic | 0.073 | Likely Benign | 0.1639 | 0.4260 | -2.04 | Neutral | 0.676 | Possibly Damaging | 0.307 | Benign | 3.75 | Benign | 0.00 | Affected | 1 | -1 | -0.8 | 10.04 | ||||||||||||||||||||||||||||||||||||
| c.259T>G | S87A 2D AIThe SynGAP1 missense variant S87A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (six benign predictions versus two pathogenic) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -7.817 | In-Between | 0.676 | Likely Pathogenic | Likely Benign | 0.039 | Likely Benign | 0.4272 | 0.3540 | -1.24 | Neutral | 0.140 | Benign | 0.097 | Benign | 3.84 | Benign | 0.00 | Affected | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||||
| c.260C>A | S87Y 2D AIThe SynGAP1 missense variant S87Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -10.410 | Likely Pathogenic | 0.986 | Likely Pathogenic | Likely Pathogenic | 0.052 | Likely Benign | 0.0522 | 0.4798 | -2.20 | Neutral | 0.880 | Possibly Damaging | 0.608 | Possibly Damaging | 3.75 | Benign | 0.00 | Affected | -3 | -2 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||||||
| c.260C>G | S87C 2D AIThe SynGAP1 missense variant S87C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is uncertain due to a 2‑to‑2 split; and Foldetta, which assesses protein‑folding stability, is unavailable for this variant. Overall, the majority of available predictions (five pathogenic versus three benign) indicate a likely pathogenic impact. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -8.769 | Likely Pathogenic | 0.915 | Likely Pathogenic | Ambiguous | 0.095 | Likely Benign | 0.0794 | 0.4849 | -2.14 | Neutral | 0.880 | Possibly Damaging | 0.700 | Possibly Damaging | 3.74 | Benign | 0.00 | Affected | 0 | -1 | 3.3 | 16.06 | ||||||||||||||||||||||||||||||||||||
| c.260C>T | S87F 2D AIThe SynGAP1 missense variant S87F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.550904 | Binding | 0.302 | 0.878 | 0.500 | -9.673 | Likely Pathogenic | 0.990 | Likely Pathogenic | Likely Pathogenic | 0.054 | Likely Benign | 0.0493 | 0.4937 | -2.34 | Neutral | 0.676 | Possibly Damaging | 0.485 | Possibly Damaging | 3.74 | Benign | 0.00 | Affected | -3 | -2 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||
| c.2632A>C | T878P 2D AIThe SynGAP1 missense variant T878P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | -3.130 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.136 | Likely Benign | 0.2026 | 0.5538 | -1.41 | Neutral | 0.761 | Possibly Damaging | 0.478 | Possibly Damaging | 2.96 | Benign | 0.01 | Affected | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||
| c.2632A>G | T878A 2D AIThe SynGAP1 missense variant T878A is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in‑silico predictors agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy tools likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is benign; Foldetta results are unavailable. Based on the unanimous benign predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | Uncertain | 1 | -2.154 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.088 | Likely Benign | 0.4312 | 0.4625 | -0.67 | Neutral | 0.003 | Benign | 0.006 | Benign | 2.73 | Benign | 0.18 | Tolerated | 3.77 | 5 | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||
| c.2632A>T | T878S 2D AIThe SynGAP1 missense variant T878S 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. 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 | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | -2.493 | Likely Benign | 0.088 | Likely Benign | Likely Benign | 0.073 | Likely Benign | 0.3557 | 0.4867 | -0.06 | Neutral | 0.009 | Benign | 0.012 | Benign | 2.82 | Benign | 0.03 | Affected | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2633C>A | T878K 2D AIThe SynGAP1 missense variant T878K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and Foldetta results are unavailable. Taken together, the majority of evidence points to a benign impact for T878K, 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 | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | -5.694 | Likely Benign | 0.592 | Likely Pathogenic | Likely Benign | 0.099 | Likely Benign | 0.1168 | 0.3300 | -1.51 | Neutral | 0.611 | Possibly Damaging | 0.196 | Benign | 2.66 | Benign | 0.00 | Affected | 0 | -1 | -3.2 | 27.07 | |||||||||||||||||||||||||||||||||||
| c.2633C>G | T878R 2D AIThe SynGAP1 missense variant T878R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | -4.289 | Likely Benign | 0.496 | Ambiguous | Likely Benign | 0.119 | Likely Benign | 0.1006 | 0.2920 | -1.39 | Neutral | 0.611 | Possibly Damaging | 0.398 | Benign | 2.64 | Benign | 0.00 | Affected | -1 | -1 | -3.8 | 55.08 | |||||||||||||||||||||||||||||||||||
| c.2633C>T | T878I 2D AIThe SynGAP1 missense variant T878I is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect. **Benign:** REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized. **Pathogenic:** polyPhen‑2 HumDiv, SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the computational evidence overwhelmingly points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.622677 | Disordered | 0.628767 | Binding | 0.288 | 0.878 | 0.250 | -6.247 | Likely Benign | 0.459 | Ambiguous | Likely Benign | 0.055 | Likely Benign | 0.0980 | 0.6502 | -1.99 | Neutral | 0.761 | Possibly Damaging | 0.398 | Benign | 2.63 | Benign | 0.00 | Affected | 0 | -1 | 5.2 | 12.05 | |||||||||||||||||||||||||||||||||||
| c.2644G>A | G882R 2D AIThe SynGAP1 missense variant G882R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -4.715 | Likely Benign | 0.758 | Likely Pathogenic | Likely Benign | 0.051 | Likely Benign | 0.0905 | 0.4126 | -1.48 | Neutral | 0.001 | Benign | 0.003 | Benign | 2.04 | Pathogenic | 0.01 | Affected | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||||
| c.2644G>C | G882R 2D AIThe SynGAP1 missense variant G882R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (six benign vs three pathogenic) support a benign classification. This consensus does not contradict any ClinVar status, as the variant is not yet catalogued there. Thus, the variant is most likely benign based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -4.715 | Likely Benign | 0.758 | Likely Pathogenic | Likely Benign | 0.051 | Likely Benign | 0.0905 | 0.4126 | -1.48 | Neutral | 0.001 | Benign | 0.003 | Benign | 2.04 | Pathogenic | 0.01 | Affected | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||||
| c.2644G>T | G882W 2D AIThe SynGAP1 missense variant G882W has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with 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 Pathogenic | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -8.637 | Likely Pathogenic | 0.606 | Likely Pathogenic | Likely Benign | 0.166 | Likely Benign | 0.0829 | 0.4616 | -2.35 | Neutral | 0.983 | Probably Damaging | 0.813 | Possibly Damaging | 2.01 | Pathogenic | 0.00 | Affected | -7 | -2 | -0.5 | 129.16 | |||||||||||||||||||||||||||||||||||
| c.2645G>A | G882E 2D AIThe SynGAP1 missense variant G882E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split; Foldetta results are unavailable. Overall, more tools (six) predict benign than pathogenic (three), and no ClinVar evidence contradicts 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. | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -4.246 | Likely Benign | 0.613 | Likely Pathogenic | Likely Benign | 0.079 | Likely Benign | 0.1263 | 0.3244 | -1.16 | Neutral | 0.004 | Benign | 0.005 | Benign | 2.04 | Pathogenic | 0.01 | Affected | 0 | -2 | -3.1 | 72.06 | ||||||||||||||||||||||||||||||||||||
| c.2645G>C | G882A 2D AIThe SynGAP1 missense variant G882A 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 predict benign, whereas only FATHMM predicts 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 results are unavailable. Overall, the majority of evidence indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -3.876 | Likely Benign | 0.131 | Likely Benign | Likely Benign | 0.048 | Likely Benign | 0.3345 | 0.5268 | -1.05 | Neutral | 0.004 | Benign | 0.002 | Benign | 2.14 | Pathogenic | 0.79 | Tolerated | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2645G>T | G882V 2D AIThe SynGAP1 missense variant G882V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.632888 | Binding | 0.306 | 0.878 | 0.250 | -5.893 | Likely Benign | 0.257 | Likely Benign | Likely Benign | 0.115 | Likely Benign | 0.1178 | 0.4717 | -2.41 | Neutral | 0.224 | Benign | 0.066 | Benign | 2.06 | Pathogenic | 0.02 | Affected | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| c.343C>A | Q115K 2D AIThe SynGAP1 missense variant Q115K 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 the overall trend. 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, a protein‑folding stability method, has no available result for this variant. Based on the preponderance of benign predictions and the high‑accuracy consensus, the variant is most likely benign; this conclusion is consistent with the absence of a ClinVar pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -3.365 | Likely Benign | 0.507 | Ambiguous | Likely Benign | 0.101 | Likely Benign | 0.1704 | 0.3678 | -0.49 | Neutral | 0.924 | Possibly Damaging | 0.857 | Possibly Damaging | 4.18 | Benign | 0.40 | Tolerated | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.343C>G | Q115E 2D AIThe SynGAP1 missense variant Q115E is reported in gnomAD (variant ID 6‑33432208‑C‑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 (both HumDiv and HumVar models) predict a pathogenic impact. 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 analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion 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 | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | 6-33432208-C-G | 1 | 6.20e-7 | -3.465 | Likely Benign | 0.229 | Likely Benign | Likely Benign | 0.096 | Likely Benign | 0.1377 | 0.1832 | -0.40 | Neutral | 0.924 | Possibly Damaging | 0.857 | Possibly Damaging | 4.18 | Benign | 0.42 | Tolerated | 3.61 | 5 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||
| c.344A>C | Q115P 2D AIThe SynGAP1 missense variant Q115P 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 assessment does not conflict with the absence of a ClinVar claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -2.766 | Likely Benign | 0.071 | Likely Benign | Likely Benign | 0.175 | Likely Benign | 0.2418 | 0.4778 | -0.71 | Neutral | 0.990 | Probably Damaging | 0.954 | Probably Damaging | 4.08 | Benign | 0.46 | Tolerated | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.344A>G | Q115R 2D AIThe SynGAP1 missense variant Q115R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors—AlphaMissense‑Optimized and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, and AlphaMissense‑Default remains uncertain. No Foldetta stability analysis is available. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a benign effect for Q115R. This assessment is consistent with the absence of a ClinVar claim, 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 | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -1.429 | Likely Benign | 0.497 | Ambiguous | Likely Benign | 0.109 | Likely Benign | 0.1469 | 0.1507 | -0.46 | Neutral | 0.967 | Probably Damaging | 0.901 | Possibly Damaging | 4.12 | Benign | 0.24 | Tolerated | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.344A>T | Q115L 2D AIThe SynGAP1 missense variant Q115L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments 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 Q115L, 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 | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -3.281 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.123 | Likely Benign | 0.0710 | 0.5452 | -1.25 | Neutral | 0.967 | Probably Damaging | 0.901 | Possibly Damaging | 4.10 | Benign | 0.10 | Tolerated | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.345G>C | Q115H 2D AIThe SynGAP1 missense variant Q115H is not reported 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. 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” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q115H, 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 | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -3.888 | Likely Benign | 0.277 | Likely Benign | Likely Benign | 0.156 | Likely Benign | 0.1248 | 0.3383 | -0.99 | Neutral | 0.990 | Probably Damaging | 0.969 | Probably Damaging | 4.08 | Benign | 0.17 | Tolerated | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.345G>T | Q115H 2D AIThe SynGAP1 missense variant Q115H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign classification for Q115H, 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 | 0.784345 | Disordered | 0.657256 | Binding | 0.327 | 0.878 | 0.750 | -3.888 | Likely Benign | 0.277 | Likely Benign | Likely Benign | 0.156 | Likely Benign | 0.1248 | 0.3383 | -0.99 | Neutral | 0.990 | Probably Damaging | 0.969 | Probably Damaging | 4.08 | Benign | 0.17 | Tolerated | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.346T>A | Y116N 2D  AIThe SynGAP1 missense variant Y116N is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | -1.706 | Likely Benign | 0.260 | Likely Benign | Likely Benign | 0.108 | Likely Benign | 0.2592 | 0.0545 | 0.21 | Neutral | 0.137 | Benign | 0.021 | Benign | 4.27 | Benign | 1.00 | Tolerated | -2 | -2 | -2.2 | -49.07 | |||||||||||||||||||||||||||||||||||
| c.346T>C | Y116H 2D  AIThe SynGAP1 missense variant Y116H is listed in gnomAD (ID 6‑33432211‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments confirm the benign trend: 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 impact, 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 | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | 6-33432211-T-C | 7 | 4.34e-6 | -1.512 | Likely Benign | 0.378 | Ambiguous | Likely Benign | 0.080 | Likely Benign | 0.2691 | 0.0485 | 0.11 | Neutral | 0.539 | Possibly Damaging | 0.085 | Benign | 4.21 | Benign | 0.40 | Tolerated | 3.61 | 5 | 2 | 0 | -1.9 | -26.03 | ||||||||||||||||||||||||||||||
| c.346T>G | Y116D 2D  AIThe SynGAP1 missense variant Y116D 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, 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 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 consensus of available predictions strongly suggests that Y116D 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 | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | 0.542 | Likely Benign | 0.524 | Ambiguous | Likely Benign | 0.302 | Likely Benign | 0.4603 | 0.0545 | -0.14 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.24 | Benign | 0.83 | Tolerated | -4 | -3 | -2.2 | -48.09 | |||||||||||||||||||||||||||||||||||
| c.347A>C | Y116S 2D  AIThe SynGAP1 missense variant Y116S 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, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that Y116S 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 | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | -0.249 | Likely Benign | 0.269 | Likely Benign | Likely Benign | 0.178 | Likely Benign | 0.5111 | 0.1694 | Weaken | -0.05 | Neutral | 0.033 | Benign | 0.013 | Benign | 4.31 | Benign | 0.58 | Tolerated | -3 | -2 | 0.5 | -76.10 | ||||||||||||||||||||||||||||||||||
| c.347A>G | Y116C 2D  AIThe SynGAP1 missense variant Y116C 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 | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | -2.822 | Likely Benign | 0.197 | Likely Benign | Likely Benign | 0.160 | Likely Benign | 0.3208 | 0.2105 | -0.90 | Neutral | 0.804 | Possibly Damaging | 0.187 | Benign | 4.19 | Benign | 0.11 | Tolerated | 0 | -2 | 3.8 | -60.04 | |||||||||||||||||||||||||||||||||||
| c.347A>T | Y116F 2D  AIThe SynGAP1 missense variant Y116F is not reported 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, 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 likelihood. 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 | 0.661982 | Disordered | 0.670235 | Binding | 0.381 | 0.878 | 0.625 | -2.911 | Likely Benign | 0.119 | Likely Benign | Likely Benign | 0.048 | Likely Benign | 0.2632 | 0.3069 | -0.71 | Neutral | 0.539 | Possibly Damaging | 0.042 | Benign | 4.21 | Benign | 0.33 | Tolerated | 7 | 3 | 4.1 | -16.00 | |||||||||||||||||||||||||||||||||||
| c.373C>A | P125T 2D AIThe SynGAP1 missense variant P125T is not 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, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | -4.780 | Likely Benign | 0.273 | Likely Benign | Likely Benign | 0.215 | Likely Benign | 0.1502 | 0.4995 | -3.78 | Deleterious | 0.036 | Benign | 0.014 | Benign | 2.85 | Benign | 0.01 | Affected | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||
| c.373C>G | P125A 2D AIThe SynGAP1 missense variant P125A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the majority of predictions and the high‑accuracy consensus, 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 | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | -3.936 | Likely Benign | 0.166 | Likely Benign | Likely Benign | 0.124 | Likely Benign | 0.3341 | 0.4245 | -3.55 | Deleterious | 0.580 | Possibly Damaging | 0.140 | Benign | 2.88 | Benign | 0.02 | Affected | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.373C>T | P125S 2D AIThe SynGAP1 missense variant P125S is listed in ClinVar (ID 837156.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, 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 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 points to a benign impact, 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 | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | Uncertain | 1 | -3.769 | Likely Benign | 0.238 | Likely Benign | Likely Benign | 0.121 | Likely Benign | 0.3408 | 0.4594 | -3.57 | Deleterious | 0.580 | Possibly Damaging | 0.140 | Benign | 2.86 | Benign | 0.02 | Affected | 3.61 | 5 | 1 | -1 | 0.8 | -10.04 | |||||||||||||||||||||||||||||||
| c.374C>A | P125H 2D  AIThe SynGAP1 missense variant P125H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the majority of conventional predictors (five pathogenic vs four benign) lean toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the inconclusive SGM Consensus temper this view. No ClinVar annotation is present, so there is no reported status to contradict the computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | -5.177 | Likely Benign | 0.583 | Likely Pathogenic | Likely Benign | 0.235 | Likely Benign | 0.1598 | 0.4263 | -4.18 | Deleterious | 0.996 | Probably Damaging | 0.750 | Possibly Damaging | 2.82 | Benign | 0.01 | Affected | 0 | -2 | -1.6 | 40.02 | ||||||||||||||||||||||||||||||||||||
| c.374C>G | P125R 2D AIThe SynGAP1 missense variant P125R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta data are unavailable. Consequently, the overall computational evidence is split evenly between benign and pathogenic predictions, with no decisive support from the most accurate methods. Based on these predictions, the variant’s impact remains inconclusive; it is neither clearly benign nor pathogenic, and this lack of consensus does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | -5.658 | Likely Benign | 0.792 | Likely Pathogenic | Ambiguous | 0.159 | Likely Benign | 0.1461 | 0.2913 | -4.33 | Deleterious | 0.952 | Possibly Damaging | 0.521 | Possibly Damaging | 2.83 | Benign | 0.09 | Tolerated | 0 | -2 | -2.9 | 59.07 | ||||||||||||||||||||||||||||||||||||
| c.374C>T | P125L 2D AIThe SynGAP1 missense variant P125L is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs 3 pathogenic, with one uncertain) points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.505461 | Disordered | 0.704227 | Binding | 0.373 | 0.878 | 0.625 | -4.565 | Likely Benign | 0.550 | Ambiguous | Likely Benign | 0.147 | Likely Benign | 0.2189 | 0.6478 | -4.82 | Deleterious | 0.906 | Possibly Damaging | 0.272 | Benign | 2.83 | Benign | 0.01 | Affected | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||
| c.382C>A | P128T 2D AIThe SynGAP1 missense variant P128T is listed in ClinVar with an “Uncertain” status (ClinVar ID 2801315.0) and is present in gnomAD (ID 6‑33432247‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | Uncertain | 1 | 6-33432247-C-A | 1 | 6.20e-7 | -4.217 | Likely Benign | 0.267 | Likely Benign | Likely Benign | 0.075 | Likely Benign | 0.2023 | 0.4053 | -0.96 | Neutral | 0.952 | Possibly Damaging | 0.500 | Possibly Damaging | 4.19 | Benign | 0.35 | Tolerated | 3.74 | 4 | -1 | 0 | 0.9 | 3.99 | ||||||||||||||||||||||||||||
| c.382C>G | P128A 2D AIThe SynGAP1 missense variant P128A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification for P128A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | -3.677 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.068 | Likely Benign | 0.3890 | 0.3353 | -0.64 | Neutral | 0.580 | Possibly Damaging | 0.140 | Benign | 4.21 | Benign | 0.75 | Tolerated | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.382C>T | P128S 2D AIThe SynGAP1 missense variant P128S is reported in gnomAD (variant ID 6‑33432247‑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 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 confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence 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 | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | 6-33432247-C-T | 1 | 6.20e-7 | -3.234 | Likely Benign | 0.268 | Likely Benign | Likely Benign | 0.084 | Likely Benign | 0.3893 | 0.3697 | -1.35 | Neutral | 0.734 | Possibly Damaging | 0.243 | Benign | 4.20 | Benign | 0.24 | Tolerated | 3.74 | 4 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||
| c.383C>A | P128H 2D AIThe SynGAP1 missense variant P128H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | -4.806 | Likely Benign | 0.564 | Ambiguous | Likely Benign | 0.169 | Likely Benign | 0.2207 | 0.3414 | -1.90 | Neutral | 0.996 | Probably Damaging | 0.750 | Possibly Damaging | 4.14 | Benign | 0.03 | Affected | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||
| c.383C>G | P128R 2D AIThe SynGAP1 missense variant P128R is not reported in ClinVar and is absent from gnomAD. Functional prediction 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. When predictions are grouped by consensus, the majority of methods (six) predict benign, while three predict pathogenic. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign effect. Foldetta results are unavailable. Overall, the computational evidence favors a benign classification for P128R, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | -5.048 | Likely Benign | 0.748 | Likely Pathogenic | Likely Benign | 0.188 | Likely Benign | 0.1810 | 0.2401 | -1.76 | Neutral | 0.984 | Probably Damaging | 0.601 | Possibly Damaging | 4.19 | Benign | 0.08 | Tolerated | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||
| c.383C>T | P128L 2D AIThe SynGAP1 missense variant P128L is catalogued in gnomAD (6‑33432248‑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). In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is reported). 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 | 0.497853 | Structured | 0.713069 | Binding | 0.376 | 0.878 | 0.625 | 6-33432248-C-T | 1 | 6.20e-7 | -4.791 | Likely Benign | 0.541 | Ambiguous | Likely Benign | 0.087 | Likely Benign | 0.2548 | 0.5137 | -0.47 | Neutral | 0.952 | Possibly Damaging | 0.500 | Possibly Damaging | 4.20 | Benign | 0.38 | Tolerated | 3.74 | 4 | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||
| c.76G>A | G26R 2D AIThe SynGAP1 missense variant G26R is listed in ClinVar as a benign alteration (ClinVar ID 1521495.0) and is present in the gnomAD database (gnomAD ID 6‑33423485‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence supports a benign impact, aligning with the ClinVar designation and indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.438291 | Uncertain | 0.351 | 0.878 | 0.375 | Benign | 1 | 6-33423485-G-A | 3 | 1.86e-6 | -2.946 | Likely Benign | 0.678 | Likely Pathogenic | Likely Benign | 0.189 | Likely Benign | 0.1097 | 0.4407 | -2.22 | Neutral | 0.994 | Probably Damaging | 0.990 | Probably Damaging | 3.87 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||
| c.76G>C | G26R 2D AIThe SynGAP1 missense variant G26R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of the four high‑accuracy tools) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy consensus—indicates that G26R is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.438291 | Uncertain | 0.351 | 0.878 | 0.375 | -2.946 | Likely Benign | 0.678 | Likely Pathogenic | Likely Benign | 0.189 | Likely Benign | 0.1097 | 0.4407 | -2.22 | Neutral | 0.994 | Probably Damaging | 0.990 | Probably Damaging | 3.87 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||
| c.77G>A | G26E 2D AIThe SynGAP1 missense variant G26E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.438291 | Uncertain | 0.351 | 0.878 | 0.375 | -3.966 | Likely Benign | 0.481 | Ambiguous | Likely Benign | 0.199 | Likely Benign | 0.1623 | 0.4238 | -2.08 | Neutral | 0.994 | Probably Damaging | 0.986 | Probably Damaging | 3.90 | Benign | 0.00 | Affected | 0 | -2 | -3.1 | 72.06 | |||||||||||||||||||||||||||||||||||
| c.77G>C | G26A 2D AIThe SynGAP1 missense variant G26A 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 G26A, 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 | 0.486429 | Structured | 0.438291 | Uncertain | 0.351 | 0.878 | 0.375 | -3.308 | Likely Benign | 0.135 | Likely Benign | Likely Benign | 0.062 | Likely Benign | 0.4093 | 0.5251 | -1.25 | Neutral | 0.953 | Possibly Damaging | 0.952 | Probably Damaging | 4.02 | Benign | 0.00 | Affected | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.77G>T | G26V 2D AIThe SynGAP1 missense variant G26V is reported in gnomAD (variant ID 6‑33423486‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicted set includes REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic‑predicted set contains polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No Foldetta stability result is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect for G26V, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.486429 | Structured | 0.438291 | Uncertain | 0.351 | 0.878 | 0.375 | 6-33423486-G-T | 1 | 6.20e-7 | -3.499 | Likely Benign | 0.165 | Likely Benign | Likely Benign | 0.197 | Likely Benign | 0.1344 | 0.4333 | -2.34 | Neutral | 0.994 | Probably Damaging | 0.990 | Probably Damaging | 3.89 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | -1 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||
| c.91C>G | R31G 2D AIThe SynGAP1 missense variant R31G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for R31G, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.437905 | Uncertain | 0.324 | 0.878 | 0.250 | -3.259 | Likely Benign | 0.269 | Likely Benign | Likely Benign | 0.141 | Likely Benign | 0.3389 | 0.3942 | -1.77 | Neutral | 0.686 | Possibly Damaging | 0.630 | Possibly Damaging | 3.97 | Benign | 0.00 | Affected | -3 | -2 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||||||
| c.92G>A | R31Q 2D AIThe SynGAP1 missense variant R31Q is listed in ClinVar (ID 1977609.0) with an “Uncertain” status and is present in gnomAD (6‑33423501‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification and suggests the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.437905 | Uncertain | 0.324 | 0.878 | 0.250 | Uncertain | 1 | 6-33423501-G-A | 7 | 4.34e-6 | -4.434 | Likely Benign | 0.136 | Likely Benign | Likely Benign | 0.051 | Likely Benign | 0.3605 | 0.3355 | -0.92 | Neutral | 0.829 | Possibly Damaging | 0.614 | Possibly Damaging | 4.01 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 1 | 1.0 | -28.06 | ||||||||||||||||||||||||||||
| c.92G>C | R31P 2D AIThe SynGAP1 missense variant R31P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign impact for R31P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.437905 | Uncertain | 0.324 | 0.878 | 0.250 | -3.185 | Likely Benign | 0.300 | Likely Benign | Likely Benign | 0.209 | Likely Benign | 0.2220 | 0.5005 | -1.64 | Neutral | 0.841 | Possibly Damaging | 0.809 | Possibly Damaging | 3.96 | Benign | 0.00 | Affected | 0 | -2 | 2.9 | -59.07 | |||||||||||||||||||||||||||||||||||
| c.92G>T | R31L 2D AIThe SynGAP1 missense variant R31L is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict pathogenic. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically indicate benign: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta data are missing. Overall, the majority of reliable predictions lean toward a benign effect, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.549308 | Disordered | 0.437905 | Uncertain | 0.324 | 0.878 | 0.250 | -3.147 | Likely Benign | 0.360 | Ambiguous | Likely Benign | 0.149 | Likely Benign | 0.2264 | 0.5148 | -1.79 | Neutral | 0.686 | Possibly Damaging | 0.630 | Possibly Damaging | 4.01 | Benign | 0.00 | Affected | -3 | -2 | 8.3 | -43.03 | |||||||||||||||||||||||||||||||||||
| c.2482A>C | T828P 2D AIThe SynGAP1 missense variant T828P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (2 benign vs. 1 pathogenic). 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. Overall, the preponderance of evidence points to a benign impact for T828P, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | -3.902 | Likely Benign | 0.466 | Ambiguous | Likely Benign | 0.280 | Likely Benign | 0.1898 | 0.4424 | -2.53 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.61 | Benign | 0.12 | Tolerated | 0 | -1 | -0.9 | -3.99 | ||||||||||||||||||||||||||||||||||||
| c.2482A>G | T828A 2D AIThe SynGAP1 missense variant T828A is reported in gnomAD (variant ID 6‑33443034‑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 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | 6-33443034-A-G | 1 | 6.20e-7 | -2.974 | Likely Benign | 0.340 | Likely Benign | Likely Benign | 0.197 | Likely Benign | 0.4039 | 0.3861 | -2.13 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.67 | Benign | 0.24 | Tolerated | 3.77 | 5 | 0 | 1 | 2.5 | -30.03 | ||||||||||||||||||||||||||||||
| c.2482A>T | T828S 2D AIThe SynGAP1 missense variant T828S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that T828S 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 | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | -2.851 | Likely Benign | 0.285 | Likely Benign | Likely Benign | 0.152 | Likely Benign | 0.3332 | 0.3913 | -0.49 | Neutral | 0.999 | Probably Damaging | 0.992 | Probably Damaging | 2.67 | Benign | 0.52 | Tolerated | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2483C>A | T828K 2D AIThe SynGAP1 missense variant T828K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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, while the SGM‑Consensus (majority vote) remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | -5.466 | Likely Benign | 0.853 | Likely Pathogenic | Ambiguous | 0.155 | Likely Benign | 0.0924 | 0.2886 | -0.88 | Neutral | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.68 | Benign | 0.39 | Tolerated | 0 | -1 | -3.2 | 27.07 | |||||||||||||||||||||||||||||||||||
| c.2483C>G | T828R 2D AIThe SynGAP1 missense variant T828R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T828R, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | -4.887 | Likely Benign | 0.773 | Likely Pathogenic | Likely Benign | 0.184 | Likely Benign | 0.0815 | 0.2530 | -1.38 | Neutral | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.64 | Benign | 0.47 | Tolerated | -1 | -1 | -3.8 | 55.08 | |||||||||||||||||||||||||||||||||||
| c.2483C>T | T828I 2D AISynGAP1 missense variant T828I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, whereas tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 split and therefore unavailable; Foldetta predictions are not provided. Consequently, the computational evidence is evenly divided between benign and pathogenic, with no clear direction. The variant is therefore not clearly benign or pathogenic based on current predictions, and this lack of consensus does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.604312 | Disordered | 0.631236 | Binding | 0.321 | 0.879 | 0.500 | -4.971 | Likely Benign | 0.893 | Likely Pathogenic | Ambiguous | 0.139 | Likely Benign | 0.0767 | 0.5262 | -3.40 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.61 | Benign | 0.06 | Tolerated | 0 | -1 | 5.2 | 12.05 | ||||||||||||||||||||||||||||||||||||
| c.2746G>A | V916I 2D  AIThe SynGAP1 missense variant V916I is reported in gnomAD (variant ID 6-33443298‑G‑A) but has no ClinVar entry. Functional prediction tools uniformly classify the change 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. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this assessment is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | 6-33443298-G-A | 25 | 1.55e-5 | -4.336 | Likely Benign | 0.074 | Likely Benign | Likely Benign | 0.062 | Likely Benign | 0.0905 | 0.4463 | -0.05 | Neutral | 0.010 | Benign | 0.015 | Benign | 2.71 | Benign | 0.09 | Tolerated | 3.77 | 5 | 3 | 4 | 0.3 | 14.03 | ||||||||||||||||||||||||||||||
| c.2746G>C | V916L 2D AIThe SynGAP1 missense variant V916L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | -2.645 | Likely Benign | 0.086 | Likely Benign | Likely Benign | 0.064 | Likely Benign | 0.1190 | 0.5323 | 0.31 | Neutral | 0.001 | Benign | 0.002 | Benign | 2.73 | Benign | 0.09 | Tolerated | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2746G>T | V916F 2D  AIThe SynGAP1 missense variant V916F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | -4.011 | Likely Benign | 0.123 | Likely Benign | Likely Benign | 0.121 | Likely Benign | 0.0729 | 0.4593 | -1.18 | Neutral | 0.642 | Possibly Damaging | 0.265 | Benign | 2.67 | Benign | 0.02 | Affected | -1 | -1 | -1.4 | 48.04 | |||||||||||||||||||||||||||||||||||
| c.2747T>A | V916D 2D  AIThe SynGAP1 missense variant V916D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic outcome. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) is not available for this variant. 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 | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | -2.653 | Likely Benign | 0.392 | Ambiguous | Likely Benign | 0.139 | Likely Benign | 0.1580 | 0.1113 | -1.48 | Neutral | 0.975 | Probably Damaging | 0.767 | Possibly Damaging | 2.69 | Benign | 0.01 | Affected | -2 | -3 | -7.7 | 15.96 | |||||||||||||||||||||||||||||||||||
| c.2747T>C | V916A 2D AIThe SynGAP1 missense variant V916A is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool in the dataset indicates a pathogenic effect, so the pathogenic‑prediction group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and the Foldetta stability analysis is not available. Based on the collective predictions, 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 | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | -2.524 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.116 | Likely Benign | 0.3455 | 0.2841 | -0.18 | Neutral | 0.244 | Benign | 0.171 | Benign | 2.91 | Benign | 1.00 | Tolerated | 0 | 0 | -2.4 | -28.05 | |||||||||||||||||||||||||||||||||||
| c.2747T>G | V916G 2D AIThe SynGAP1 missense variant V916G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) 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. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.642678 | Disordered | 0.835395 | Binding | 0.308 | 0.879 | 0.250 | -1.950 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.093 | Likely Benign | 0.2420 | 0.2681 | -0.63 | Neutral | 0.666 | Possibly Damaging | 0.917 | Probably Damaging | 2.69 | Benign | 0.05 | Affected | -1 | -3 | -4.6 | -42.08 | ||||||||||||||||||||||||||||||||||||
| 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 | 0.2153 | 0.3788 | -0.84 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.89 | Tolerated | 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 | 0.2504 | 0.3066 | -1.09 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.05 | Benign | 0.93 | Tolerated | 4.32 | 2 | -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 | 0.1465 | 0.4506 | -1.27 | Neutral | 0.878 | Possibly Damaging | 0.232 | Benign | 4.01 | Benign | 0.23 | Tolerated | 4.32 | 2 | 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 | 0.2168 | 0.4301 | -0.27 | Neutral | 0.001 | Benign | 0.001 | Benign | 4.01 | Benign | 0.72 | Tolerated | 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 | 0.2198 | 0.3410 | -0.71 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.06 | Benign | 0.69 | Tolerated | 4.32 | 2 | 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 | 0.1514 | 0.5316 | -1.74 | Neutral | 0.174 | Benign | 0.062 | Benign | 4.05 | Benign | 0.35 | Tolerated | -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 | 0.2058 | 0.3914 | -0.66 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.45 | Tolerated | 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 | 0.2058 | 0.3914 | -0.66 | Neutral | 0.748 | Possibly Damaging | 0.232 | Benign | 4.06 | Benign | 0.45 | Tolerated | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| c.3409C>A | H1137N 2D AIThe SynGAP1 missense variant H1137N 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 | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -3.105 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.208 | Likely Benign | 0.1983 | 0.3638 | -1.53 | Neutral | 0.625 | Possibly Damaging | 0.353 | Benign | 5.34 | Benign | 0.00 | Affected | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||
| c.3409C>G | H1137D 2D AIThe SynGAP1 missense variant H1137D is not reported in ClinVar and has no allele in gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Pathogenicity is suggested only by polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for H1137D, 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 | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -4.934 | Likely Benign | 0.343 | Ambiguous | Likely Benign | 0.418 | Likely Benign | 0.2519 | 0.2916 | -2.26 | Neutral | 0.802 | Possibly Damaging | 0.430 | Benign | 5.56 | Benign | 0.00 | Affected | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||
| c.3409C>T | H1137Y 2D AIThe SynGAP1 missense variant H1137Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for H1137Y, 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 | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -4.506 | Likely Benign | 0.124 | Likely Benign | Likely Benign | 0.310 | Likely Benign | 0.1073 | 0.5123 | -1.93 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 5.28 | Benign | 0.00 | Affected | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||
| c.340A>C | K114Q 2D  AIThe SynGAP1 missense variant K114Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -3.221 | Likely Benign | 0.467 | Ambiguous | Likely Benign | 0.058 | Likely Benign | 0.5476 | 0.1530 | Weaken | -1.33 | Neutral | 0.608 | Possibly Damaging | 0.108 | Benign | 3.98 | Benign | 0.00 | Affected | 1 | 1 | 0.4 | -0.04 | ||||||||||||||||||||||||||||||||||
| c.340A>G | K114E 2D  AISynGAP1 missense variant K114E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while AlphaMissense‑Optimized is uncertain. 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) 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, as none exists for K114E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -2.648 | Likely Benign | 0.885 | Likely Pathogenic | Ambiguous | 0.093 | Likely Benign | 0.4815 | 0.1340 | -1.27 | Neutral | 0.005 | Benign | 0.003 | Benign | 4.01 | Benign | 0.00 | Affected | 0 | 1 | 0.4 | 0.94 | |||||||||||||||||||||||||||||||||||
| c.3410A>C | H1137P 2D AIThe SynGAP1 missense variant H1137P is listed in ClinVar as a benign alteration (ClinVar ID 3685596.0) and is present in the gnomAD database (gnomAD ID 6‑33444445‑A‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same four high‑accuracy predictors) also indicates benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions, including the most reliable tools, support a benign classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | Benign | 1 | 6-33444445-A-C | 12 | 7.44e-6 | -2.098 | Likely Benign | 0.054 | Likely Benign | Likely Benign | 0.419 | Likely Benign | 0.2045 | 0.4501 | -1.93 | Neutral | 0.925 | Possibly Damaging | 0.703 | Possibly Damaging | 5.29 | Benign | 0.00 | Affected | 4.32 | 4 | -2 | 0 | 1.6 | -40.02 | ||||||||||||||||||||||||||||
| c.3410A>G | H1137R 2D AIThe SynGAP1 missense variant H1137R is reported in gnomAD (ID 6‑33444445‑A‑G) 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, 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 (majority vote) also indicates Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | 6-33444445-A-G | 1 | 6.20e-7 | -3.468 | Likely Benign | 0.228 | Likely Benign | Likely Benign | 0.296 | Likely Benign | 0.2131 | 0.3449 | -1.19 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 5.32 | Benign | 0.00 | Affected | 4.32 | 4 | 0 | 2 | -1.3 | 19.05 | ||||||||||||||||||||||||||||||
| c.3410A>T | H1137L 2D AIThe SynGAP1 missense variant H1137L 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 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 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 | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -2.215 | Likely Benign | 0.080 | Likely Benign | Likely Benign | 0.359 | Likely Benign | 0.1199 | 0.6082 | -2.77 | Deleterious | 0.802 | Possibly Damaging | 0.534 | Possibly Damaging | 5.30 | Benign | 0.00 | Affected | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||
| c.3411T>A | H1137Q 2D AIThe SynGAP1 missense variant H1137Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational 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 | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -2.958 | Likely Benign | 0.110 | Likely Benign | Likely Benign | 0.239 | Likely Benign | 0.1873 | 0.4090 | -1.19 | Neutral | 0.925 | Possibly Damaging | 0.703 | Possibly Damaging | 5.34 | Benign | 0.00 | Affected | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| c.3411T>G | H1137Q 2D AIThe SynGAP1 missense variant H1137Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for H1137Q, 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 | 0.903857 | Disordered | 0.756488 | Binding | 0.314 | 0.879 | 0.875 | -2.958 | Likely Benign | 0.110 | Likely Benign | Likely Benign | 0.239 | Likely Benign | 0.1873 | 0.4090 | -1.19 | Neutral | 0.925 | Possibly Damaging | 0.703 | Possibly Damaging | 5.34 | Benign | 0.00 | Affected | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| c.341A>C | K114T 2D  AIThe SynGAP1 missense variant K114T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively indicate a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM‑Consensus score is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -3.366 | Likely Benign | 0.804 | Likely Pathogenic | Ambiguous | 0.091 | Likely Benign | 0.2796 | 0.3391 | -1.48 | Neutral | 0.759 | Possibly Damaging | 0.190 | Benign | 3.95 | Benign | 0.00 | Affected | 0 | -1 | 3.2 | -27.07 | |||||||||||||||||||||||||||||||||||
| c.341A>G | K114R 2D  AIThe SynGAP1 missense variant K114R is not reported 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; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -1.861 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.041 | Likely Benign | 0.5668 | 0.1498 | Weaken | -1.02 | Neutral | 0.005 | Benign | 0.003 | Benign | 4.09 | Benign | 0.00 | Affected | 3 | 2 | -0.6 | 28.01 | ||||||||||||||||||||||||||||||||||
| c.341A>T | K114M 2D  AIThe SynGAP1 missense variant K114M is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points toward a benign effect, and there is no ClinVar entry to contradict this conclusion. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -3.953 | Likely Benign | 0.877 | Likely Pathogenic | Ambiguous | 0.120 | Likely Benign | 0.1809 | 0.4075 | -1.89 | Neutral | 0.992 | Probably Damaging | 0.615 | Possibly Damaging | 3.90 | Benign | 0.00 | Affected | 0 | -1 | 5.8 | 3.02 | |||||||||||||||||||||||||||||||||||
| c.342G>C | K114N 2D  AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -3.851 | Likely Benign | 0.937 | Likely Pathogenic | Ambiguous | 0.045 | Likely Benign | 0.4590 | 0.1877 | -1.41 | Neutral | 0.608 | Possibly Damaging | 0.190 | Benign | 3.95 | Benign | 0.00 | Affected | 1 | 0 | 0.4 | -14.07 | |||||||||||||||||||||||||||||||||||
| c.342G>T | K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.754692 | Disordered | 0.649749 | Binding | 0.381 | 0.879 | 0.750 | -3.851 | Likely Benign | 0.937 | Likely Pathogenic | Ambiguous | 0.045 | Likely Benign | 0.4590 | 0.1877 | -1.41 | Neutral | 0.608 | Possibly Damaging | 0.190 | Benign | 3.95 | Benign | 0.00 | Affected | 1 | 0 | 0.4 | -14.07 | |||||||||||||||||||||||||||||||||||
| 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 | 0.2546 | 0.4935 | -2.45 | Neutral | 0.127 | Benign | 0.045 | Benign | 4.08 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.1018 | 0.3791 | -2.17 | Neutral | 0.834 | Possibly Damaging | 0.307 | Benign | 4.04 | Benign | 0.00 | Affected | -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 | 0.1345 | 0.3753 | -3.83 | Deleterious | 0.939 | Possibly Damaging | 0.570 | Possibly Damaging | 3.99 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.2115 | 0.2859 | -3.54 | Deleterious | 0.588 | Possibly Damaging | 0.212 | Benign | 4.03 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.3582 | 0.4284 | -2.62 | Deleterious | 0.001 | Benign | 0.002 | Benign | 4.08 | Benign | 0.00 | Affected | 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 | 0.1132 | 0.3635 | -2.99 | Deleterious | 0.004 | Benign | 0.004 | Benign | 4.05 | Benign | 0.00 | Affected | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| c.94A>C | T32P 2D AIThe SynGAP1 missense variant T32P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, two tools—polyPhen‑2 HumDiv and SIFT—classify the change as pathogenic. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, and this 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 | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | -2.958 | Likely Benign | 0.055 | Likely Benign | Likely Benign | 0.102 | Likely Benign | 0.2327 | 0.5818 | -0.94 | Neutral | 0.604 | Possibly Damaging | 0.185 | Benign | 4.14 | Benign | 0.00 | Affected | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||
| c.94A>G | T32A 2D AIThe SynGAP1 missense variant T32A 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 consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | -3.330 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.047 | Likely Benign | 0.4174 | 0.4742 | -0.63 | Neutral | 0.043 | Benign | 0.016 | Benign | 4.21 | Benign | 0.00 | Affected | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.94A>T | T32S 2D AIThe SynGAP1 missense variant T32S 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 consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | -2.618 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.062 | Likely Benign | 0.3603 | 0.5174 | -0.39 | Neutral | 0.171 | Benign | 0.050 | Benign | 4.18 | Benign | 0.00 | Affected | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.95C>A | T32N 2D  AIThe SynGAP1 missense variant T32N is catalogued in gnomAD (ID 6‑33423504‑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, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: 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 reported result for this variant, so its status is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | 6-33423504-C-A | 2 | 1.24e-6 | -3.466 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.040 | Likely Benign | 0.1681 | 0.5264 | -1.01 | Neutral | 0.604 | Possibly Damaging | 0.140 | Benign | 4.15 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 0 | -2.8 | 13.00 | ||||||||||||||||||||||||||||||
| c.95C>G | T32S 2D AIThe SynGAP1 missense variant T32S 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 consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | -2.618 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.024 | Likely Benign | 0.3603 | 0.5174 | -0.39 | Neutral | 0.171 | Benign | 0.050 | Benign | 4.18 | Benign | 0.00 | Affected | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.95C>T | T32I 2D AIThe SynGAP1 missense variant T32I is reported in gnomAD (ID 6‑33423504‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also reports likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for T32I, 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 | 0.707965 | Disordered | 0.437154 | Uncertain | 0.349 | 0.879 | 0.375 | 6-33423504-C-T | 1 | 6.20e-7 | -3.689 | Likely Benign | 0.213 | Likely Benign | Likely Benign | 0.024 | Likely Benign | 0.1081 | 0.6403 | -0.57 | Neutral | 0.049 | Benign | 0.026 | Benign | 4.26 | Benign | 0.00 | Affected | 4.32 | 1 | -1 | 0 | 5.2 | 12.05 | ||||||||||||||||||||||||||||||
| c.2743G>A | G915S 2D AIThe SynGAP1 missense variant G915S is listed in ClinVar as Benign (ClinVar ID 652083.0) and is present in the gnomAD database (gnomAD ID 6‑33443295‑G‑A). 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 reports a pathogenic prediction, representing the sole discordant signal. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | Benign | 1 | 6-33443295-G-A | 9 | 5.58e-6 | -3.557 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.050 | Likely Benign | 0.2393 | 0.4875 | -0.88 | Neutral | 0.801 | Possibly Damaging | 0.201 | Benign | 2.73 | Benign | 0.31 | Tolerated | 3.77 | 5 | 1 | 0 | -0.4 | 30.03 | ||||||||||||||||||||||||||||
| c.2743G>C | G915R 2D AIThe SynGAP1 missense variant G915R is 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 evidence points to a benign impact for G915R, 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 | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | -4.528 | Likely Benign | 0.656 | Likely Pathogenic | Likely Benign | 0.104 | Likely Benign | 0.0805 | 0.4204 | -2.31 | Neutral | 0.999 | Probably Damaging | 0.969 | Probably Damaging | 2.69 | Benign | 0.00 | Affected | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.2743G>T | G915C 2D AIThe SynGAP1 missense variant G915C is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6-33443295-G‑T). Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | 6-33443295-G-T | 1 | 6.20e-7 | -6.446 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.103 | Likely Benign | 0.1023 | 0.4471 | -2.84 | Deleterious | 1.000 | Probably Damaging | 0.989 | Probably Damaging | 2.64 | Benign | 0.01 | Affected | 3.77 | 5 | -3 | -3 | 2.9 | 46.09 | ||||||||||||||||||||||||||||||
| c.2744G>A | G915D 2D AIThe SynGAP1 missense variant G915D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G915D, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | -3.409 | Likely Benign | 0.502 | Ambiguous | Likely Benign | 0.134 | Likely Benign | 0.1574 | 0.1559 | -1.75 | Neutral | 0.978 | Probably Damaging | 0.871 | Possibly Damaging | 2.70 | Benign | 0.01 | Affected | 1 | -1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||
| c.2744G>C | G915A 2D AIThe SynGAP1 missense variant G915A 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 returns Benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect for G915A, 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 | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | -4.007 | Likely Benign | 0.103 | Likely Benign | Likely Benign | 0.053 | Likely Benign | 0.3454 | 0.4930 | -1.22 | Neutral | 0.900 | Possibly Damaging | 0.622 | Possibly Damaging | 2.87 | Benign | 0.05 | Affected | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2744G>T | G915V 2D AIThe SynGAP1 missense variant G915V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (6‑33443296‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign; the Foldetta stability analysis is unavailable. Overall, the majority of predictions, including the most reliable tools, indicate a benign impact. This consensus does not contradict ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.657645 | Disordered | 0.808641 | Binding | 0.302 | 0.880 | 0.375 | 6-33443296-G-T | -4.586 | Likely Benign | 0.189 | Likely Benign | Likely Benign | 0.149 | Likely Benign | 0.0927 | 0.4291 | -2.52 | Deleterious | 0.997 | Probably Damaging | 0.918 | Probably Damaging | 2.68 | Benign | 0.01 | Affected | 3.77 | 5 | -3 | -1 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||
| c.298T>A | Y100N 2D AIThe SynGAP1 missense variant Y100N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | -2.579 | Likely Benign | 0.109 | Likely Benign | Likely Benign | 0.183 | Likely Benign | 0.2487 | 0.0373 | -0.66 | Neutral | 0.675 | Possibly Damaging | 0.099 | Benign | 4.23 | Benign | 0.00 | Affected | -2 | -2 | -2.2 | -49.07 | |||||||||||||||||||||||||||||||||||
| c.298T>C | Y100H 2D AIThe SynGAP1 missense variant Y100H is reported in gnomAD (variant ID 6-33432163‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicted set includes REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic‑predicted set contains polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments reinforce the benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign verdict. 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 Y100H is most likely benign, and this conclusion is not contradicted by any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | 6-33432163-T-C | 1 | 6.20e-7 | -2.094 | Likely Benign | 0.201 | Likely Benign | Likely Benign | 0.123 | Likely Benign | 0.2650 | 0.0313 | -0.40 | Neutral | 0.978 | Probably Damaging | 0.500 | Possibly Damaging | 4.23 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 0 | -1.9 | -26.03 | ||||||||||||||||||||||||||||||
| c.298T>G | Y100D 2D AIThe SynGAP1 missense variant Y100D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is 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 | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | -1.269 | Likely Benign | 0.215 | Likely Benign | Likely Benign | 0.233 | Likely Benign | 0.4465 | 0.0373 | -1.01 | Neutral | 0.003 | Benign | 0.003 | Benign | 4.22 | Benign | 0.00 | Affected | -4 | -3 | -2.2 | -48.09 | |||||||||||||||||||||||||||||||||||
| c.299A>C | Y100S 2D AIThe SynGAP1 missense variant Y100S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | -1.217 | Likely Benign | 0.129 | Likely Benign | Likely Benign | 0.182 | Likely Benign | 0.5066 | 0.1600 | Weaken | -0.14 | Neutral | 0.675 | Possibly Damaging | 0.175 | Benign | 4.31 | Benign | 0.00 | Affected | -3 | -2 | 0.5 | -76.10 | ||||||||||||||||||||||||||||||||||
| c.299A>G | Y100C 2D AIThe SynGAP1 missense variant Y100C 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 | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | -3.789 | Likely Benign | 0.117 | Likely Benign | Likely Benign | 0.172 | Likely Benign | 0.3073 | 0.2213 | -0.88 | Neutral | 0.994 | Probably Damaging | 0.816 | Possibly Damaging | 4.18 | Benign | 0.00 | Affected | 0 | -2 | 3.8 | -60.04 | |||||||||||||||||||||||||||||||||||
| c.299A>T | Y100F 2D AIThe SynGAP1 missense variant Y100F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.699094 | Disordered | 0.675421 | Binding | 0.341 | 0.880 | 0.625 | -3.056 | Likely Benign | 0.117 | Likely Benign | Likely Benign | 0.139 | Likely Benign | 0.2784 | 0.3087 | -0.50 | Neutral | 0.928 | Possibly Damaging | 0.222 | Benign | 4.21 | Benign | 0.00 | Affected | 7 | 3 | 4.1 | -16.00 | |||||||||||||||||||||||||||||||||||
| c.3319C>A | Q1107K 2D AIThe SynGAP1 missense variant Q1107K 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 the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Only polyPhen‑2 HumDiv predicts a pathogenic effect, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments further reinforce the 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 impact, 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 | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -4.066 | Likely Benign | 0.400 | Ambiguous | Likely Benign | 0.095 | Likely Benign | 0.1805 | 0.5276 | -1.99 | Neutral | 0.920 | Possibly Damaging | 0.425 | Benign | 2.60 | Benign | 0.30 | Tolerated | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.3319C>G | Q1107E 2D AIThe SynGAP1 missense variant Q1107E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion 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 | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -3.875 | Likely Benign | 0.231 | Likely Benign | Likely Benign | 0.076 | Likely Benign | 0.1453 | 0.2932 | -1.54 | Neutral | 0.920 | Possibly Damaging | 0.425 | Benign | 2.59 | Benign | 0.02 | Affected | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.3320A>C | Q1107P 2D AIThe SynGAP1 missense variant Q1107P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect for Q1107P, 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 | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -2.643 | Likely Benign | 0.047 | Likely Benign | Likely Benign | 0.135 | Likely Benign | 0.2109 | 0.5767 | -2.35 | Neutral | 0.965 | Probably Damaging | 0.611 | Possibly Damaging | 2.57 | Benign | 0.01 | Affected | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.3320A>G | Q1107R 2D AIThe SynGAP1 missense variant Q1107R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -2.837 | Likely Benign | 0.394 | Ambiguous | Likely Benign | 0.126 | Likely Benign | 0.1482 | 0.3319 | -1.76 | Neutral | 0.965 | Probably Damaging | 0.425 | Benign | 2.55 | Benign | 0.04 | Affected | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.3320A>T | Q1107L 2D AIThe SynGAP1 missense variant Q1107L 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, 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 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. | Likely Benign | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -3.785 | Likely Benign | 0.116 | Likely Benign | Likely Benign | 0.119 | Likely Benign | 0.0820 | 0.6447 | -3.27 | Deleterious | 0.006 | Benign | 0.004 | Benign | 2.53 | Benign | 0.01 | Affected | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.3321G>C | Q1107H 2D AIThe SynGAP1 missense variant Q1107H 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -3.546 | Likely Benign | 0.260 | Likely Benign | Likely Benign | 0.136 | Likely Benign | 0.1514 | 0.4683 | -2.58 | Deleterious | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.51 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.3321G>T | Q1107H 2D AIThe SynGAP1 missense variant Q1107H 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 show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, while Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.876521 | Disordered | 0.951017 | Binding | 0.393 | 0.880 | 0.875 | -3.546 | Likely Benign | 0.260 | Likely Benign | Likely Benign | 0.136 | Likely Benign | 0.1514 | 0.4683 | -2.58 | Deleterious | 0.990 | Probably Damaging | 0.796 | Possibly Damaging | 2.51 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.385T>A | S129T 2D AIThe SynGAP1 missense variant S129T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, 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 any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.713635 | Binding | 0.311 | 0.880 | 0.625 | -4.296 | Likely Benign | 0.171 | Likely Benign | Likely Benign | 0.134 | Likely Benign | 0.1251 | 0.5794 | 0.12 | Neutral | 0.016 | Benign | 0.021 | Benign | 4.14 | Benign | 0.85 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.385T>C | S129P 2D AIThe SynGAP1 missense variant S129P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, 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 | 0.517562 | Disordered | 0.713635 | Binding | 0.311 | 0.880 | 0.625 | -2.469 | Likely Benign | 0.237 | Likely Benign | Likely Benign | 0.220 | Likely Benign | 0.1998 | 0.4989 | -0.09 | Neutral | 0.454 | Possibly Damaging | 0.133 | Benign | 4.11 | Benign | 0.32 | Tolerated | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||
| c.385T>G | S129A 2D AIThe SynGAP1 missense variant S129A 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 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 predicts benign, and the SGM‑Consensus itself is 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 | 0.517562 | Disordered | 0.713635 | Binding | 0.311 | 0.880 | 0.625 | -3.388 | Likely Benign | 0.134 | Likely Benign | Likely Benign | 0.090 | Likely Benign | 0.5031 | 0.4619 | Weaken | -0.08 | Neutral | 0.007 | Benign | 0.007 | Benign | 4.21 | Benign | 0.15 | Tolerated | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||
| c.386C>G | S129W 2D AIThe SynGAP1 missense variant S129W is not reported 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 high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.713635 | Binding | 0.311 | 0.880 | 0.625 | -5.008 | Likely Benign | 0.824 | Likely Pathogenic | Ambiguous | 0.108 | Likely Benign | 0.0523 | 0.5471 | -1.49 | Neutral | 0.888 | Possibly Damaging | 0.367 | Benign | 4.06 | Benign | 0.01 | Affected | -2 | -3 | -0.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.386C>T | S129L 2D AIThe SynGAP1 missense variant S129L is catalogued in gnomAD (ID 6‑33432251‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all report benign or likely benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence indicates that S129L is most likely benign, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.713635 | Binding | 0.311 | 0.880 | 0.625 | 6-33432251-C-T | 1 | 6.20e-7 | -4.487 | Likely Benign | 0.456 | Ambiguous | Likely Benign | 0.256 | Likely Benign | 0.0885 | 0.5249 | -0.18 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.14 | Benign | 0.05 | Affected | 3.74 | 4 | -2 | -3 | 4.6 | 26.08 | ||||||||||||||||||||||||||||||
| c.2464A>C | T822P 2D AIThe SynGAP1 missense variant T822P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T822P. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | -3.961 | Likely Benign | 0.737 | Likely Pathogenic | Likely Benign | 0.145 | Likely Benign | 0.2437 | 0.5044 | -2.29 | Neutral | 0.999 | Probably Damaging | 0.985 | Probably Damaging | 2.50 | Benign | 0.09 | Tolerated | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||
| c.2464A>G | T822A 2D AIThe SynGAP1 T822A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus (majority vote) remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | -3.695 | Likely Benign | 0.788 | Likely Pathogenic | Ambiguous | 0.122 | Likely Benign | 0.4566 | 0.4456 | -1.55 | Neutral | 0.987 | Probably Damaging | 0.891 | Possibly Damaging | 2.60 | Benign | 0.17 | Tolerated | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.2464A>T | T822S 2D AIThe SynGAP1 missense variant T822S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T822S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | -1.710 | Likely Benign | 0.655 | Likely Pathogenic | Likely Benign | 0.107 | Likely Benign | 0.3794 | 0.4547 | -0.54 | Neutral | 0.998 | Probably Damaging | 0.949 | Probably Damaging | 3.08 | Benign | 0.74 | Tolerated | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2465C>A | T822K 2D AIThe SynGAP1 missense variant T822K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of conventional tools lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction contradicts this. Because ClinVar has no entry for this variant, there is no existing clinical classification to conflict with; thus, the variant is most likely benign based on the preponderance of evidence, though high‑accuracy predictions remain inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | -1.814 | Likely Benign | 0.977 | Likely Pathogenic | Likely Pathogenic | 0.215 | Likely Benign | 0.1369 | 0.3552 | -2.25 | Neutral | 1.000 | Probably Damaging | 0.988 | Probably Damaging | 2.51 | Benign | 0.07 | Tolerated | 0 | -1 | -3.2 | 27.07 | |||||||||||||||||||||||||||||||||||
| c.2465C>G | T822R 2D AIThe SynGAP1 missense variant T822R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (five pathogenic versus three benign predictions) suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | 0.414 | Likely Benign | 0.952 | Likely Pathogenic | Ambiguous | 0.237 | Likely Benign | 0.1182 | 0.3439 | -2.74 | Deleterious | 1.000 | Probably Damaging | 0.992 | Probably Damaging | 2.50 | Benign | 0.05 | Affected | -1 | -1 | -3.8 | 55.08 | ||||||||||||||||||||||||||||||||||||
| c.2465C>T | T822M 2D  AIThe SynGAP1 missense variant T822M is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443017‑C‑T). 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. AlphaMissense‑Optimized is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and 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 pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.724957 | Disordered | 0.651624 | Binding | 0.295 | 0.881 | 0.750 | 6-33443017-C-T | 5 | 3.10e-6 | -4.525 | Likely Benign | 0.833 | Likely Pathogenic | Ambiguous | 0.239 | Likely Benign | 0.1580 | 0.6379 | -2.11 | Neutral | 1.000 | Probably Damaging | 0.989 | Probably Damaging | 2.48 | Pathogenic | 0.03 | Affected | 3.77 | 5 | -1 | -1 | 2.6 | 30.09 | |||||||||||||||||||||||||||||||
| c.3028T>A | F1010I 2D AIThe SynGAP1 missense variant F1010I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict 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 | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -3.726 | Likely Benign | 0.664 | Likely Pathogenic | Likely Benign | 0.126 | Likely Benign | 0.2405 | 0.2464 | -1.74 | Neutral | 0.980 | Probably Damaging | 0.783 | Possibly Damaging | 2.57 | Benign | 0.05 | Affected | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.3028T>C | F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently 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 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 | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -1.982 | Likely Benign | 0.949 | Likely Pathogenic | Ambiguous | 0.099 | Likely Benign | 0.2538 | 0.3245 | -1.51 | Neutral | 0.910 | Possibly Damaging | 0.468 | Possibly Damaging | 2.75 | Benign | 0.62 | Tolerated | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.3028T>G | F1010V 2D AIThe SynGAP1 missense variant F1010V is not reported in ClinVar (no ClinVar ID) 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 effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the 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 (majority vote) also indicates benign. Foldetta results are unavailable. Overall, the balance of evidence from multiple independent predictors and the consensus analysis points to a benign classification for F1010V, with no conflict with ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -2.482 | Likely Benign | 0.582 | Likely Pathogenic | Likely Benign | 0.113 | Likely Benign | 0.2351 | 0.2403 | -2.10 | Neutral | 0.961 | Probably Damaging | 0.721 | Possibly Damaging | 2.58 | Benign | 0.03 | Affected | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||
| c.3029T>A | F1010Y 2D AIThe SynGAP1 missense variant F1010Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -3.297 | Likely Benign | 0.138 | Likely Benign | Likely Benign | 0.071 | Likely Benign | 0.1651 | 0.2514 | -0.96 | Neutral | 0.031 | Benign | 0.064 | Benign | 2.64 | Benign | 0.05 | Affected | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.3029T>C | F1010S 2D AIThe SynGAP1 missense variant F1010S is listed in gnomAD (ID 6‑33443581‑T‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are unavailable. Overall, the balance of evidence, including the high‑accuracy benign predictions and the consensus benign call, indicates that the variant is most likely benign. 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 | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | 6-33443581-T-C | -1.722 | Likely Benign | 0.744 | Likely Pathogenic | Likely Benign | 0.153 | Likely Benign | 0.4196 | 0.0775 | -1.97 | Neutral | 0.994 | Probably Damaging | 0.892 | Possibly Damaging | 2.51 | Benign | 0.01 | Affected | 3.77 | 5 | -2 | -3 | -3.6 | -60.10 | ||||||||||||||||||||||||||||||||
| c.3029T>G | F1010C 2D AIThe SynGAP1 missense variant F1010C is not 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 assessment shows AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -4.442 | Likely Benign | 0.755 | Likely Pathogenic | Likely Benign | 0.153 | Likely Benign | 0.2646 | 0.1605 | -2.31 | Neutral | 1.000 | Probably Damaging | 0.961 | Probably Damaging | 2.48 | Pathogenic | 0.00 | Affected | -4 | -2 | -0.3 | -44.04 | ||||||||||||||||||||||||||||||||||||
| c.3030T>A | F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently 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 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 | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -1.982 | Likely Benign | 0.949 | Likely Pathogenic | Ambiguous | 0.142 | Likely Benign | 0.2538 | 0.3245 | -1.51 | Neutral | 0.910 | Possibly Damaging | 0.468 | Possibly Damaging | 2.75 | Benign | 0.62 | Tolerated | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.3030T>G | F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign classification, 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 not contradicted by ClinVar, which has no entry for F1010L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.741537 | Disordered | 0.912572 | Binding | 0.286 | 0.881 | 0.625 | -1.982 | Likely Benign | 0.949 | Likely Pathogenic | Ambiguous | 0.142 | Likely Benign | 0.2538 | 0.3245 | -1.51 | Neutral | 0.910 | Possibly Damaging | 0.468 | Possibly Damaging | 2.75 | Benign | 0.62 | Tolerated | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.355G>A | E119K 2D AIThe SynGAP1 missense variant E119K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. Overall, the majority of high‑accuracy predictors (including the SGM‑Consensus) indicate a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -6.741 | Likely Benign | 0.922 | Likely Pathogenic | Ambiguous | 0.122 | Likely Benign | 0.2633 | 0.7739 | -1.95 | Neutral | 0.012 | Benign | 0.006 | Benign | 3.85 | Benign | 0.01 | Affected | 0 | 1 | -0.4 | -0.94 | |||||||||||||||||||||||||||||||||||
| c.355G>C | E119Q 2D AIThe SynGAP1 missense variant E119Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments therefore favor a benign effect: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates that E119Q is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -5.839 | Likely Benign | 0.676 | Likely Pathogenic | Likely Benign | 0.136 | Likely Benign | 0.1627 | 0.7886 | -1.38 | Neutral | 0.596 | Possibly Damaging | 0.143 | Benign | 3.84 | Benign | 0.02 | Affected | 2 | 2 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||
| c.356A>C | E119A 2D AIThe SynGAP1 missense variant E119A is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence (five benign versus three pathogenic predictions) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -4.881 | Likely Benign | 0.647 | Likely Pathogenic | Likely Benign | 0.108 | Likely Benign | 0.4374 | 0.7514 | -2.52 | Deleterious | 0.231 | Benign | 0.074 | Benign | 3.84 | Benign | 0.01 | Affected | 0 | -1 | 5.3 | -58.04 | ||||||||||||||||||||||||||||||||||||
| c.356A>G | E119G 2D AIThe SynGAP1 missense variant E119G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -4.349 | Likely Benign | 0.584 | Likely Pathogenic | Likely Benign | 0.143 | Likely Benign | 0.3246 | 0.6405 | -2.40 | Neutral | 0.421 | Benign | 0.055 | Benign | 3.82 | Benign | 0.01 | Affected | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||
| c.356A>T | E119V 2D AISynGAP1 missense variant E119V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, ESM1b, FATHMM, and polyPhen‑2 HumVar, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy methods are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie and is therefore unavailable, and Foldetta results are not provided. Consequently, the evidence does not strongly support either outcome. The variant is most likely inconclusive; it does not clearly favor benign or pathogenic status, and this lack of consensus does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -5.696 | Likely Benign | 0.842 | Likely Pathogenic | Ambiguous | 0.151 | Likely Benign | 0.1152 | 0.7753 | -2.78 | Deleterious | 0.596 | Possibly Damaging | 0.189 | Benign | 3.79 | Benign | 0.00 | Affected | -2 | -2 | 7.7 | -29.98 | ||||||||||||||||||||||||||||||||||||
| c.357G>C | E119D 2D AIThe SynGAP1 missense variant E119D is not reported in ClinVar and is absent from 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 all return benign scores. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are 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 | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | -3.258 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.033 | Likely Benign | 0.2180 | 0.5759 | 0.07 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.08 | Benign | 0.32 | Tolerated | 3.61 | 5 | 2 | 3 | 0.0 | -14.03 | 10.1016/j.ajhg.2020.11.011 | ||||||||||||||||||||||||||||||||
| c.357G>T | E119D 2D AIThe SynGAP1 missense variant E119D is reported in gnomAD (variant ID 6‑33432222‑G‑T) but 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 concur: AlphaMissense‑Optimized indicates a benign effect, 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, did not provide a result for this variant. Overall, the evidence strongly supports a benign classification, 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 | 0.690604 | Disordered | 0.661946 | Binding | 0.346 | 0.881 | 0.750 | 6-33432222-G-T | 3 | 1.86e-6 | -3.258 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.033 | Likely Benign | 0.2180 | 0.5759 | 0.07 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.08 | Benign | 0.32 | Tolerated | 3.61 | 5 | 2 | 3 | 0.0 | -14.03 | 10.1016/j.ajhg.2020.11.011 | |||||||||||||||||||||||||||||
| c.79C>A | P27T 2D AIThe SynGAP1 missense variant P27T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including high‑accuracy tools, points to a benign effect for P27T, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | -3.612 | Likely Benign | 0.103 | Likely Benign | Likely Benign | 0.106 | Likely Benign | 0.2430 | 0.5923 | -2.07 | Neutral | 0.909 | Possibly Damaging | 0.901 | Possibly Damaging | 3.85 | Benign | 0.00 | Affected | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||
| c.79C>G | P27A 2D AIThe SynGAP1 missense variant P27A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including high‑accuracy tools, points to a benign effect for P27A, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | -3.409 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.077 | Likely Benign | 0.4041 | 0.5219 | -1.98 | Neutral | 0.805 | Possibly Damaging | 0.857 | Possibly Damaging | 3.90 | Benign | 0.00 | Affected | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.79C>T | P27S 2D AIThe SynGAP1 missense variant P27S is reported in gnomAD (ID 6‑33423488‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (derived from the majority of these high‑accuracy predictors) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that P27S is most likely benign, and this assessment does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | 6-33423488-C-T | 1 | 6.20e-7 | -2.891 | Likely Benign | 0.098 | Likely Benign | Likely Benign | 0.063 | Likely Benign | 0.3916 | 0.5443 | -2.01 | Neutral | 0.909 | Possibly Damaging | 0.901 | Possibly Damaging | 3.91 | Benign | 0.00 | Affected | 4.32 | 1 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||
| c.80C>A | P27H 2D AIThe SynGAP1 missense variant P27H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for P27H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | -4.116 | Likely Benign | 0.177 | Likely Benign | Likely Benign | 0.128 | Likely Benign | 0.2384 | 0.5290 | -2.46 | Neutral | 0.992 | Probably Damaging | 0.977 | Probably Damaging | 3.79 | Benign | 0.00 | Affected | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||
| c.80C>G | P27R 2D AIThe SynGAP1 missense variant P27R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for P27R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | -3.260 | Likely Benign | 0.268 | Likely Benign | Likely Benign | 0.146 | Likely Benign | 0.1744 | 0.4203 | -2.28 | Neutral | 0.972 | Probably Damaging | 0.954 | Probably Damaging | 3.82 | Benign | 0.00 | Affected | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||
| c.80C>T | P27L 2D AIThe SynGAP1 missense variant P27L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.517562 | Disordered | 0.437871 | Uncertain | 0.430 | 0.881 | 0.375 | -3.297 | Likely Benign | 0.161 | Likely Benign | Likely Benign | 0.174 | Likely Benign | 0.2684 | 0.6161 | -2.59 | Deleterious | 0.909 | Possibly Damaging | 0.927 | Probably Damaging | 3.82 | Benign | 0.00 | Affected | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||
| c.2329C>A | L777I 2D  AIThe SynGAP1 missense variant L777I is listed in gnomAD (ID 6‑33442487‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which reports “Likely Benign.” Pathogenic predictions are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. 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. 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 classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | 6-33442487-C-A | -5.346 | Likely Benign | 0.128 | Likely Benign | Likely Benign | 0.096 | Likely Benign | 0.1041 | 0.4327 | -0.85 | Neutral | 0.843 | Possibly Damaging | 0.920 | Probably Damaging | 4.05 | Benign | 0.02 | Affected | 3.64 | 6 | 2 | 2 | 0.7 | 0.00 | ||||||||||||||||||||||||||||||||
| c.2329C>G | L777V 2D AIThe SynGAP1 missense variant L777V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | -5.693 | Likely Benign | 0.134 | Likely Benign | Likely Benign | 0.084 | Likely Benign | 0.1651 | 0.3977 | -1.05 | Neutral | 0.843 | Possibly Damaging | 0.920 | Probably Damaging | 4.07 | Benign | 0.05 | Affected | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2329C>T | L777F 2D AIThe SynGAP1 missense variant L777F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | -4.499 | Likely Benign | 0.175 | Likely Benign | Likely Benign | 0.115 | Likely Benign | 0.0697 | 0.3576 | -1.91 | Neutral | 0.968 | Probably Damaging | 0.966 | Probably Damaging | 3.98 | Benign | 0.01 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||
| c.2330T>A | L777H 2D  AIThe SynGAP1 missense variant L777H has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence—including the consensus of high‑accuracy tools—suggests that the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | -6.719 | Likely Benign | 0.492 | Ambiguous | Likely Benign | 0.230 | Likely Benign | 0.1052 | 0.0972 | -2.51 | Deleterious | 0.997 | Probably Damaging | 0.993 | Probably Damaging | 3.95 | Benign | 0.00 | Affected | -2 | -3 | -7.0 | 23.98 | ||||||||||||||||||||||||||||||||||||
| c.2330T>C | L777P 2D AIThe SynGAP1 missense variant L777P is catalogued in gnomAD (6‑33442488‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | 6-33442488-T-C | -5.807 | Likely Benign | 0.361 | Ambiguous | Likely Benign | 0.255 | Likely Benign | 0.3732 | 0.1664 | -2.13 | Neutral | 0.991 | Probably Damaging | 0.985 | Probably Damaging | 3.94 | Benign | 0.00 | Affected | 3.64 | 6 | -3 | -3 | -5.4 | -16.04 | ||||||||||||||||||||||||||||||||
| c.2330T>G | L777R 2D AIThe SynGAP1 missense variant L777R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.408655 | Structured | 0.876129 | Binding | 0.336 | 0.882 | 0.250 | -6.084 | Likely Benign | 0.650 | Likely Pathogenic | Likely Benign | 0.227 | Likely Benign | 0.1249 | 0.0846 | -2.20 | Neutral | 0.991 | Probably Damaging | 0.985 | Probably Damaging | 3.97 | Benign | 0.00 | Affected | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||
| c.2485G>A | E829K 2D AIThe SynGAP1 missense variant E829K is listed in ClinVar as Pathogenic (ClinVar ID 1721258.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only REVEL predicts a benign outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E829K is most likely pathogenic, and this conclusion aligns with the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | Pathogenic | 1 | -7.527 | In-Between | 0.807 | Likely Pathogenic | Ambiguous | 0.194 | Likely Benign | 0.2400 | 0.7372 | -2.65 | Deleterious | 0.994 | Probably Damaging | 0.900 | Possibly Damaging | 2.27 | Pathogenic | 0.00 | Affected | 3.77 | 5 | 0 | 1 | -0.4 | -0.94 | |||||||||||||||||||||||||||||||
| c.2485G>C | E829Q 2D AIThe SynGAP1 missense variant E829Q is not 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, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of reliable tools predict a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -4.985 | Likely Benign | 0.531 | Ambiguous | Likely Benign | 0.225 | Likely Benign | 0.1321 | 0.7248 | -1.83 | Neutral | 0.994 | Probably Damaging | 0.946 | Probably Damaging | 2.26 | Pathogenic | 0.00 | Affected | 2 | 2 | 0.0 | -0.98 | ||||||||||||||||||||||||||||||||||||
| c.2486A>C | E829A 2D AIThe SynGAP1 missense variant E829A is not 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. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Overall, the majority of evidence—including the SGM‑Consensus—points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -4.096 | Likely Benign | 0.574 | Likely Pathogenic | Likely Benign | 0.265 | Likely Benign | 0.4707 | 0.7255 | -3.75 | Deleterious | 0.994 | Probably Damaging | 0.926 | Probably Damaging | 2.26 | Pathogenic | 0.00 | Affected | 0 | -1 | 5.3 | -58.04 | |||||||||||||||||||||||||||||||||||
| c.2486A>G | E829G 2D AIThe SynGAP1 missense variant E829G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, 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 Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, with one high‑accuracy tool suggesting benign. No ClinVar annotation exists, so there is no contradiction with clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -4.152 | Likely Benign | 0.593 | Likely Pathogenic | Likely Benign | 0.316 | Likely Benign | 0.3517 | 0.6557 | -4.52 | Deleterious | 0.994 | Probably Damaging | 0.927 | Probably Damaging | 2.24 | Pathogenic | 0.00 | Affected | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||
| c.2486A>T | E829V 2D AIThe SynGAP1 missense variant E829V is not 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. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority of the four high‑accuracy inputs) remains pathogenic; 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. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -5.142 | Likely Benign | 0.719 | Likely Pathogenic | Likely Benign | 0.296 | Likely Benign | 0.0835 | 0.7984 | -4.86 | Deleterious | 0.999 | Probably Damaging | 0.977 | Probably Damaging | 2.21 | Pathogenic | 0.00 | Affected | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||
| c.2487G>C | E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that E829D 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 | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -4.015 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.066 | Likely Benign | 0.1939 | 0.4964 | -1.89 | Neutral | 0.217 | Benign | 0.121 | Benign | 2.40 | Pathogenic | 0.00 | Affected | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2487G>T | E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that E829D 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 | 0.562014 | Disordered | 0.626045 | Binding | 0.326 | 0.882 | 0.375 | -4.015 | Likely Benign | 0.091 | Likely Benign | Likely Benign | 0.066 | Likely Benign | 0.1939 | 0.4964 | -1.89 | Neutral | 0.217 | Benign | 0.121 | Benign | 2.40 | Pathogenic | 0.00 | Affected | 3 | 2 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||||
| 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 | 0.2360 | 0.3838 | -0.50 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.09 | Benign | 0.80 | Tolerated | 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 | 0.2697 | 0.3066 | -0.94 | Neutral | 0.007 | Benign | 0.018 | Benign | 4.09 | Benign | 0.62 | Tolerated | 3.77 | 5 | -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 | 0.1582 | 0.4906 | -1.02 | Neutral | 0.327 | Benign | 0.147 | Benign | 4.03 | Benign | 0.25 | Tolerated | 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 | 0.2342 | 0.4901 | -0.69 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.06 | Benign | 0.19 | Tolerated | 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 | 0.2394 | 0.3610 | -0.88 | Neutral | 0.065 | Benign | 0.049 | Benign | 4.08 | Benign | 0.38 | Tolerated | 3.77 | 5 | 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 | 0.1606 | 0.5338 | -1.66 | Neutral | 0.033 | Benign | 0.018 | Benign | 4.06 | Benign | 1.00 | Tolerated | -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 | 0.2257 | 0.3936 | -0.71 | Neutral | 0.138 | Benign | 0.105 | Benign | 4.09 | Benign | 0.28 | Tolerated | 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 | 0.2257 | 0.3936 | -0.71 | Neutral | 0.138 | Benign | 0.105 | Benign | 4.09 | Benign | 0.28 | Tolerated | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| c.3133G>A | A1045T 2D AIThe SynGAP1 missense variant A1045T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | -4.531 | Likely Benign | 0.074 | Likely Benign | Likely Benign | 0.059 | Likely Benign | 0.1857 | 0.6682 | 0.03 | Neutral | 0.004 | Benign | 0.010 | Benign | 2.68 | Benign | 0.52 | Tolerated | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.3133G>C | A1045P 2D AIThe SynGAP1 missense variant A1045P 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 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, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | -2.260 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.099 | Likely Benign | 0.2130 | 0.5332 | 1.09 | Neutral | 0.586 | Possibly Damaging | 0.223 | Benign | 2.64 | Benign | 0.24 | Tolerated | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.3133G>T | A1045S 2D AIThe SynGAP1 missense variant A1045S 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, 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 | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | -3.724 | Likely Benign | 0.073 | Likely Benign | Likely Benign | 0.055 | Likely Benign | 0.2648 | 0.5493 | -0.11 | Neutral | 0.011 | Benign | 0.010 | Benign | 2.66 | Benign | 0.46 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.3134C>A | A1045D 2D AIThe SynGAP1 missense variant A1045D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the variant as benign. AlphaMissense‑Optimized also predicts a benign outcome, whereas AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” No tools predict pathogenicity. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective predictions strongly suggest that A1045D is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | -5.734 | Likely Benign | 0.418 | Ambiguous | Likely Benign | 0.066 | Likely Benign | 0.1954 | 0.2102 | -1.00 | Neutral | 0.411 | Benign | 0.172 | Benign | 2.64 | Benign | 0.16 | Tolerated | 0 | -2 | -5.3 | 44.01 | |||||||||||||||||||||||||||||||||||
| c.3134C>G | A1045G 2D AIThe SynGAP1 missense variant A1045G is reported in ClinVar as Benign (ClinVar ID 416778.0) and is present in the gnomAD database (gnomAD ID 6‑33443686‑C‑G). Prediction tools that assess pathogenicity all converge on a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | Benign/Likely benign | 7 | 6-33443686-C-G | 1407 | 8.72e-4 | -3.246 | Likely Benign | 0.075 | Likely Benign | Likely Benign | 0.024 | Likely Benign | 0.2246 | 0.4798 | -1.21 | Neutral | 0.224 | Benign | 0.066 | Benign | 2.64 | Benign | 0.33 | Tolerated | 3.77 | 5 | 1 | 0 | -2.2 | -14.03 | 10.1016/j.ajhg.2020.11.011 | |||||||||||||||||||||||||||
| c.3134C>T | A1045V 2D AIThe SynGAP1 missense variant A1045V 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 | 0.975609 | Disordered | 0.948874 | Binding | 0.352 | 0.882 | 0.750 | -4.229 | Likely Benign | 0.076 | Likely Benign | Likely Benign | 0.035 | Likely Benign | 0.1487 | 0.5474 | -0.35 | Neutral | 0.011 | Benign | 0.017 | Benign | 3.06 | Benign | 1.00 | Tolerated | 0 | 0 | 2.4 | 28.05 | |||||||||||||||||||||||||||||||||||
| c.2305C>A | L769I 2D AIThe SynGAP1 missense variant L769I is listed in gnomAD (ID 6‑33442463‑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 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 | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | 6-33442463-C-A | -3.993 | Likely Benign | 0.110 | Likely Benign | Likely Benign | 0.099 | Likely Benign | 0.0800 | 0.3108 | -0.15 | Neutral | 0.836 | Possibly Damaging | 0.329 | Benign | 4.09 | Benign | 0.04 | Affected | 3.64 | 6 | 2 | 2 | 0.7 | 0.00 | ||||||||||||||||||||||||||||||||
| c.2305C>G | L769V 2D AIThe SynGAP1 missense variant L769V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | -4.585 | Likely Benign | 0.106 | Likely Benign | Likely Benign | 0.075 | Likely Benign | 0.1364 | 0.2558 | -0.41 | Neutral | 0.625 | Possibly Damaging | 0.249 | Benign | 4.04 | Benign | 0.25 | Tolerated | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2305C>T | L769F 2D AIThe SynGAP1 missense variant L769F is listed in ClinVar (ID 3617309.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions—including the high‑accuracy tools—suggest the variant is most likely benign, which is consistent with its ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | Uncertain | 1 | -5.044 | Likely Benign | 0.146 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.0554 | 0.2881 | -0.89 | Neutral | 0.925 | Possibly Damaging | 0.510 | Possibly Damaging | 3.94 | Benign | 0.02 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||
| c.2306T>A | L769H 2D AIThe SynGAP1 missense variant L769H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which classify the variant as benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, all of which report the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | -6.038 | Likely Benign | 0.422 | Ambiguous | Likely Benign | 0.235 | Likely Benign | 0.1016 | 0.0828 | -1.96 | Neutral | 0.977 | Probably Damaging | 0.721 | Possibly Damaging | 3.90 | Benign | 0.00 | Affected | -2 | -3 | -7.0 | 23.98 | |||||||||||||||||||||||||||||||||||
| c.2306T>C | L769P 2D AIThe SynGAP1 missense variant L769P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | -6.261 | Likely Benign | 0.338 | Likely Benign | Likely Benign | 0.200 | Likely Benign | 0.3573 | 0.1323 | -1.75 | Neutral | 0.925 | Possibly Damaging | 0.427 | Benign | 3.90 | Benign | 0.00 | Affected | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||
| c.2306T>G | L769R 2D AIThe SynGAP1 missense variant L769R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.411940 | Structured | 0.928432 | Binding | 0.367 | 0.883 | 0.250 | -6.245 | Likely Benign | 0.493 | Ambiguous | Likely Benign | 0.206 | Likely Benign | 0.1286 | 0.0702 | -1.66 | Neutral | 0.003 | Benign | 0.006 | Benign | 3.91 | Benign | 0.00 | Affected | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||
| c.2311T>A | S771T 2D AIThe SynGAP1 missense variant S771T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign impact. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -4.765 | Likely Benign | 0.112 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.1497 | 0.6310 | -1.38 | Neutral | 0.649 | Possibly Damaging | 0.433 | Benign | 4.07 | Benign | 0.23 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2311T>C | S771P 2D AIThe SynGAP1 missense variant S771P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -5.045 | Likely Benign | 0.112 | Likely Benign | Likely Benign | 0.180 | Likely Benign | 0.2194 | 0.5515 | -1.32 | Neutral | 0.901 | Possibly Damaging | 0.692 | Possibly Damaging | 4.03 | Benign | 0.19 | Tolerated | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||
| c.2311T>G | S771A 2D AIThe SynGAP1 missense variant S771A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -4.337 | Likely Benign | 0.107 | Likely Benign | Likely Benign | 0.067 | Likely Benign | 0.5201 | 0.4745 | Weaken | -1.09 | Neutral | 0.025 | Benign | 0.014 | Benign | 4.09 | Benign | 0.62 | Tolerated | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||
| c.2312C>A | S771Y 2D AIThe SynGAP1 missense variant S771Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -7.041 | In-Between | 0.397 | Ambiguous | Likely Benign | 0.176 | Likely Benign | 0.0707 | 0.5155 | -2.13 | Neutral | 0.990 | Probably Damaging | 0.892 | Possibly Damaging | 4.02 | Benign | 0.05 | Affected | -3 | -2 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||||||
| c.2312C>G | S771C 2D AIThe SynGAP1 missense variant S771C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -8.014 | Likely Pathogenic | 0.167 | Likely Benign | Likely Benign | 0.177 | Likely Benign | 0.1022 | 0.5899 | -1.99 | Neutral | 0.990 | Probably Damaging | 0.917 | Probably Damaging | 4.01 | Benign | 0.07 | Tolerated | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2312C>T | S771F 2D AIThe SynGAP1 missense variant S771F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.436924 | Structured | 0.922503 | Binding | 0.306 | 0.883 | 0.250 | -7.988 | In-Between | 0.525 | Ambiguous | Likely Benign | 0.189 | Likely Benign | 0.0624 | 0.5428 | -2.29 | Neutral | 0.990 | Probably Damaging | 0.892 | Possibly Damaging | 4.02 | Benign | 0.04 | Affected | -3 | -2 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||
| c.2338T>A | S780T 2D AIThe SynGAP1 missense variant S780T is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | -4.911 | Likely Benign | 0.157 | Likely Benign | Likely Benign | 0.048 | Likely Benign | 0.1445 | 0.6631 | -0.63 | Neutral | 0.951 | Possibly Damaging | 0.614 | Possibly Damaging | 2.66 | Benign | 0.84 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2338T>C | S780P 2D AIThe SynGAP1 missense variant S780P is reported in gnomAD (ID 6‑33442890‑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. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | 6-33442890-T-C | 1 | 6.22e-7 | -6.055 | Likely Benign | 0.234 | Likely Benign | Likely Benign | 0.088 | Likely Benign | 0.2086 | 0.6171 | -1.11 | Neutral | 0.995 | Probably Damaging | 0.892 | Possibly Damaging | 2.64 | Benign | 0.30 | Tolerated | 3.64 | 6 | -1 | 1 | -0.8 | 10.04 | ||||||||||||||||||||||||||||||
| c.2338T>G | S780A 2D AIThe SynGAP1 missense variant S780A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S780A is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | -5.627 | Likely Benign | 0.164 | Likely Benign | Likely Benign | 0.072 | Likely Benign | 0.4936 | 0.5522 | -0.40 | Neutral | 0.798 | Possibly Damaging | 0.340 | Benign | 2.69 | Benign | 0.74 | Tolerated | 1 | 1 | 2.6 | -16.00 | |||||||||||||||||||||||||||||||||||
| c.2339C>A | S780Y 2D AIThe SynGAP1 missense variant S780Y is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | -7.682 | In-Between | 0.656 | Likely Pathogenic | Likely Benign | 0.091 | Likely Benign | 0.0810 | 0.6428 | -1.71 | Neutral | 0.995 | Probably Damaging | 0.925 | Probably Damaging | 2.61 | Benign | 0.11 | Tolerated | -3 | -2 | -0.5 | 76.10 | ||||||||||||||||||||||||||||||||||||
| c.2339C>G | S780C 2D AIThe SynGAP1 missense variant S780C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442891‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a pathogenic outcome; ESM1b is inconclusive and therefore treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are not reported and thus unavailable. Based on the collective predictions, the variant is most likely benign, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | Uncertain | 4 | 6-33442891-C-G | 16 | 9.94e-6 | -7.603 | In-Between | 0.278 | Likely Benign | Likely Benign | 0.078 | Likely Benign | 0.1063 | 0.6581 | -1.41 | Neutral | 0.065 | Benign | 0.043 | Benign | 2.59 | Benign | 0.10 | Tolerated | 3.64 | 6 | -1 | 0 | 3.3 | 16.06 | ||||||||||||||||||||||||||||
| c.2339C>T | S780F 2D AIThe SynGAP1 missense variant S780F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is also unavailable for this variant. Overall, the majority of available predictions (five benign vs. four pathogenic) lean toward a benign impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.599170 | Disordered | 0.812415 | Binding | 0.283 | 0.883 | 0.500 | -8.055 | Likely Pathogenic | 0.677 | Likely Pathogenic | Likely Benign | 0.104 | Likely Benign | 0.0768 | 0.6706 | -1.42 | Neutral | 0.995 | Probably Damaging | 0.925 | Probably Damaging | 2.61 | Benign | 0.10 | Tolerated | -3 | -2 | 3.6 | 60.10 | ||||||||||||||||||||||||||||||||||||
| c.2344G>A | D782N 2D AIThe SynGAP1 missense variant D782N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -6.857 | Likely Benign | 0.766 | Likely Pathogenic | Likely Benign | 0.131 | Likely Benign | 0.1167 | 0.6884 | -2.26 | Neutral | 0.995 | Probably Damaging | 0.950 | Probably Damaging | 1.98 | Pathogenic | 0.02 | Affected | 2 | 1 | 0.0 | -0.98 | ||||||||||||||||||||||||||||||||||||
| c.2344G>C | D782H 2D AIThe SynGAP1 missense variant D782H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only REVEL predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta data are unavailable. Taken together, the majority of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -8.528 | Likely Pathogenic | 0.937 | Likely Pathogenic | Ambiguous | 0.311 | Likely Benign | 0.1333 | 0.7286 | -2.63 | Deleterious | 1.000 | Probably Damaging | 0.989 | Probably Damaging | 1.93 | Pathogenic | 0.00 | Affected | 1 | -1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||
| c.2344G>T | D782Y 2D AIThe SynGAP1 missense variant D782Y is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -8.785 | Likely Pathogenic | 0.919 | Likely Pathogenic | Ambiguous | 0.382 | Likely Benign | 0.0559 | 0.6202 | -3.75 | Deleterious | 1.000 | Probably Damaging | 0.989 | Probably Damaging | 1.91 | Pathogenic | 0.00 | Affected | -4 | -3 | 2.2 | 48.09 | |||||||||||||||||||||||||||||||||||
| c.2345A>C | D782A 2D AIThe SynGAP1 missense variant D782A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, reports the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Taken together, the preponderance of evidence from multiple in silico predictors and the SGM‑Consensus suggests that D782A is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -7.054 | In-Between | 0.892 | Likely Pathogenic | Ambiguous | 0.345 | Likely Benign | 0.3819 | 0.6121 | -3.33 | Deleterious | 0.990 | Probably Damaging | 0.932 | Probably Damaging | 1.95 | Pathogenic | 0.01 | Affected | 0 | -2 | 5.3 | -44.01 | |||||||||||||||||||||||||||||||||||
| c.2345A>G | D782G 2D AIThe SynGAP1 missense variant D782G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -6.811 | Likely Benign | 0.858 | Likely Pathogenic | Ambiguous | 0.291 | Likely Benign | 0.3816 | 0.6318 | -3.27 | Deleterious | 0.995 | Probably Damaging | 0.950 | Probably Damaging | 1.95 | Pathogenic | 0.02 | Affected | 1 | -1 | 3.1 | -58.04 | |||||||||||||||||||||||||||||||||||
| c.2345A>T | D782V 2D AIThe SynGAP1 missense variant D782V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which reports “Likely Pathogenic”). The high‑accuracy AlphaMissense‑Optimized tool yields an uncertain result, and the Foldetta stability assessment is unavailable. Overall, the consensus of the available predictions strongly favors a pathogenic effect for D782V. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -8.250 | Likely Pathogenic | 0.931 | Likely Pathogenic | Ambiguous | 0.462 | Likely Benign | 0.0803 | 0.6477 | -3.59 | Deleterious | 0.999 | Probably Damaging | 0.979 | Probably Damaging | 1.92 | Pathogenic | 0.00 | Affected | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||
| c.2346C>A | D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -4.447 | Likely Benign | 0.486 | Ambiguous | Likely Benign | 0.127 | Likely Benign | 0.1351 | 0.7036 | -1.75 | Neutral | 0.561 | Possibly Damaging | 0.207 | Benign | 2.14 | Pathogenic | 0.01 | Affected | 3 | 2 | 0.0 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2346C>G | D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a majority benign vote (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.604312 | Disordered | 0.768342 | Binding | 0.285 | 0.883 | 0.625 | -4.447 | Likely Benign | 0.486 | Ambiguous | Likely Benign | 0.127 | Likely Benign | 0.1351 | 0.7036 | -1.75 | Neutral | 0.561 | Possibly Damaging | 0.207 | Benign | 2.14 | Pathogenic | 0.01 | Affected | 3 | 2 | 0.0 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2458T>A | Y820N 2D AIThe SynGAP1 Y820N variant is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default all predict a pathogenic outcome. AlphaMissense‑Optimized returns an “Uncertain” result. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are evenly split between benign and pathogenic, with no high‑confidence pathogenic or benign signal. Thus, the variant is most likely of uncertain significance, which is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | Uncertain | 1 | -9.032 | Likely Pathogenic | 0.842 | Likely Pathogenic | Ambiguous | 0.143 | Likely Benign | 0.2352 | 0.0704 | -1.53 | Neutral | 0.999 | Probably Damaging | 0.977 | Probably Damaging | 2.74 | Benign | 0.20 | Tolerated | -2 | -2 | -2.2 | -49.07 | ||||||||||||||||||||||||||||||||||
| c.2458T>C | Y820H 2D AIThe SynGAP1 missense variant Y820H is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443010‑T‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | 6-33443010-T-C | 5 | 3.10e-6 | -7.432 | In-Between | 0.928 | Likely Pathogenic | Ambiguous | 0.129 | Likely Benign | 0.2498 | 0.0704 | -0.13 | Neutral | 0.999 | Probably Damaging | 0.989 | Probably Damaging | 2.70 | Benign | 0.24 | Tolerated | 3.77 | 5 | 2 | 0 | -1.9 | -26.03 | |||||||||||||||||||||||||||||||
| c.2458T>G | Y820D 2D AIThe SynGAP1 missense variant Y820D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that Y820D is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | -10.497 | Likely Pathogenic | 0.963 | Likely Pathogenic | Likely Pathogenic | 0.169 | Likely Benign | 0.4113 | 0.0704 | -2.77 | Deleterious | 0.999 | Probably Damaging | 0.977 | Probably Damaging | 2.73 | Benign | 0.08 | Tolerated | -4 | -3 | -2.2 | -48.09 | |||||||||||||||||||||||||||||||||||
| c.2459A>C | Y820S 2D AIThe SynGAP1 missense variant Y820S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for Y820S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | -7.094 | In-Between | 0.723 | Likely Pathogenic | Likely Benign | 0.101 | Likely Benign | 0.5166 | 0.2291 | Weaken | -1.79 | Neutral | 0.999 | Probably Damaging | 0.951 | Probably Damaging | 2.80 | Benign | 0.22 | Tolerated | -3 | -2 | 0.5 | -76.10 | |||||||||||||||||||||||||||||||||||
| c.2459A>G | Y820C 2D AIThe SynGAP1 missense variant Y820C is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence—including the SGM‑Consensus—suggests the variant is most likely pathogenic, a conclusion that does not contradict the current ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | Uncertain | 1 | -8.797 | Likely Pathogenic | 0.744 | Likely Pathogenic | Likely Benign | 0.113 | Likely Benign | 0.3177 | 0.1915 | -3.16 | Deleterious | 1.000 | Probably Damaging | 0.983 | Probably Damaging | 2.68 | Benign | 0.06 | Tolerated | 3.77 | 5 | 0 | -2 | 3.8 | -60.04 | |||||||||||||||||||||||||||||||
| c.2459A>T | Y820F 2D AIThe SynGAP1 missense variant Y820F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for Y820F, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.733139 | Disordered | 0.695550 | Binding | 0.293 | 0.883 | 0.625 | -4.686 | Likely Benign | 0.301 | Likely Benign | Likely Benign | 0.111 | Likely Benign | 0.2398 | 0.2636 | -1.67 | Neutral | 0.990 | Probably Damaging | 0.893 | Possibly Damaging | 2.69 | Benign | 0.21 | Tolerated | 7 | 3 | 4.1 | -16.00 | |||||||||||||||||||||||||||||||||||
| c.2461T>A | C821S 2D  AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -0.425 | Likely Benign | 0.898 | Likely Pathogenic | Ambiguous | 0.190 | Likely Benign | 0.5284 | 0.2012 | Weaken | -0.47 | Neutral | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.91 | Benign | 1.00 | Tolerated | 0 | -1 | -3.3 | -16.06 | ||||||||||||||||||||||||||||||||||
| c.2461T>C | C821R 2D  AIThe SynGAP1 missense variant C821R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, while three suggest benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -3.997 | Likely Benign | 0.993 | Likely Pathogenic | Likely Pathogenic | 0.183 | Likely Benign | 0.1944 | 0.1746 | -2.93 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.69 | Benign | 0.03 | Affected | -4 | -3 | -7.0 | 53.05 | ||||||||||||||||||||||||||||||||||||
| c.2461T>G | C821G 2D  AIThe SynGAP1 missense variant C821G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -4.613 | Likely Benign | 0.910 | Likely Pathogenic | Ambiguous | 0.187 | Likely Benign | 0.3287 | 0.2747 | -2.94 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.68 | Benign | 0.05 | Affected | -3 | -3 | -2.9 | -46.09 | ||||||||||||||||||||||||||||||||||||
| c.2462G>A | C821Y 2D  AIThe SynGAP1 missense variant C821Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools support pathogenicity while three support benignity, and no high‑accuracy consensus contradicts this trend. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -1.007 | Likely Benign | 0.982 | Likely Pathogenic | Likely Pathogenic | 0.342 | Likely Benign | 0.1288 | 0.3187 | -3.11 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.66 | Benign | 0.01 | Affected | 0 | -2 | -3.8 | 60.04 | ||||||||||||||||||||||||||||||||||||
| c.2462G>C | C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -0.425 | Likely Benign | 0.898 | Likely Pathogenic | Ambiguous | 0.314 | Likely Benign | 0.5284 | 0.2012 | Weaken | -0.47 | Neutral | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.91 | Benign | 1.00 | Tolerated | 0 | -1 | -3.3 | -16.06 | ||||||||||||||||||||||||||||||||||
| c.2462G>T | C821F 2D  AIThe SynGAP1 missense variant C821F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | 0.971 | Likely Benign | 0.924 | Likely Pathogenic | Ambiguous | 0.338 | Likely Benign | 0.1504 | 0.3505 | -3.33 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.66 | Benign | 0.01 | Affected | -4 | -2 | 0.3 | 44.04 | ||||||||||||||||||||||||||||||||||||
| c.2463C>G | C821W 2D  AIThe SynGAP1 missense variant C821W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.745909 | Disordered | 0.672821 | Binding | 0.351 | 0.883 | 0.750 | -4.843 | Likely Benign | 0.993 | Likely Pathogenic | Likely Pathogenic | 0.201 | Likely Benign | 0.1742 | 0.3268 | -3.30 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.64 | Benign | 0.01 | Affected | -8 | -2 | -3.4 | 83.07 | ||||||||||||||||||||||||||||||||||||
| 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 | 0.2430 | 0.7825 | -0.22 | Neutral | 0.561 | Possibly Damaging | 0.139 | Benign | 2.72 | Benign | 0.81 | Tolerated | 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 | 0.2792 | 0.8228 | -1.74 | Neutral | 1.000 | Probably Damaging | 0.975 | Probably Damaging | 2.68 | Benign | 0.13 | Tolerated | 3.77 | 5 | -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 | 0.1305 | 0.7494 | -2.52 | Deleterious | 1.000 | Probably Damaging | 0.983 | Probably Damaging | 2.67 | Benign | 0.05 | Affected | -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 | 0.4296 | 0.7244 | -1.45 | Neutral | 0.995 | Probably Damaging | 0.895 | Possibly Damaging | 2.76 | Benign | 0.10 | Tolerated | 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 | 0.4313 | 0.7006 | -0.93 | Neutral | 0.990 | Probably Damaging | 0.817 | Possibly Damaging | 2.82 | Benign | 0.72 | Tolerated | 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 | 0.1766 | 0.7408 | -2.21 | Neutral | 1.000 | Probably Damaging | 0.977 | Probably Damaging | 2.70 | Benign | 0.02 | Affected | -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 | 0.2524 | 0.6915 | -1.07 | Neutral | 0.990 | Probably Damaging | 0.801 | Possibly Damaging | 2.76 | Benign | 0.15 | Tolerated | 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 | 0.2524 | 0.6915 | -1.07 | Neutral | 0.990 | Probably Damaging | 0.801 | Possibly Damaging | 2.76 | Benign | 0.15 | Tolerated | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2812G>A | G938R 2D AIThe SynGAP1 missense variant G938R is listed in ClinVar (ID 1019898.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑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 (seven benign versus three pathogenic predictions) supports a benign classification. This consensus does not contradict the ClinVar “Uncertain” designation, which remains unresolved. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | Uncertain | 1 | -5.271 | Likely Benign | 0.732 | Likely Pathogenic | Likely Benign | 0.141 | Likely Benign | 0.0924 | 0.3614 | -1.11 | Neutral | 0.999 | Probably Damaging | 0.985 | Probably Damaging | 2.74 | Benign | 0.36 | Tolerated | 3.77 | 5 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||
| c.2812G>C | G938R 2D AIThe SynGAP1 missense variant G938R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign” call. 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, 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 | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | -5.271 | Likely Benign | 0.732 | Likely Pathogenic | Likely Benign | 0.141 | Likely Benign | 0.0924 | 0.3614 | -1.11 | Neutral | 0.999 | Probably Damaging | 0.985 | Probably Damaging | 2.74 | Benign | 0.36 | Tolerated | 3.77 | 5 | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||
| c.2812G>T | G938W 2D AIThe SynGAP1 missense variant G938W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, 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 due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | -8.763 | Likely Pathogenic | 0.604 | Likely Pathogenic | Likely Benign | 0.194 | Likely Benign | 0.0762 | 0.4008 | -1.71 | Neutral | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.70 | Benign | 0.04 | Affected | -7 | -2 | -0.5 | 129.16 | ||||||||||||||||||||||||||||||||||||
| c.2813G>A | G938E 2D AIThe SynGAP1 missense variant G938E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status 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 | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | -5.394 | Likely Benign | 0.577 | Likely Pathogenic | Likely Benign | 0.112 | Likely Benign | 0.1370 | 0.3720 | -1.40 | Neutral | 0.997 | Probably Damaging | 0.979 | Probably Damaging | 2.75 | Benign | 0.28 | Tolerated | 0 | -2 | -3.1 | 72.06 | |||||||||||||||||||||||||||||||||||
| c.2813G>C | G938A 2D AIThe SynGAP1 missense variant G938A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta’s protein‑folding stability analysis is not 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 | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | -5.068 | Likely Benign | 0.139 | Likely Benign | Likely Benign | 0.095 | Likely Benign | 0.3462 | 0.4948 | -0.41 | Neutral | 0.979 | Probably Damaging | 0.821 | Possibly Damaging | 2.80 | Benign | 0.82 | Tolerated | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2813G>T | G938V 2D AIThe SynGAP1 missense variant G938V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that G938V is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.905695 | Disordered | 0.949795 | Binding | 0.318 | 0.883 | 0.625 | -6.112 | Likely Benign | 0.153 | Likely Benign | Likely Benign | 0.123 | Likely Benign | 0.1230 | 0.3811 | -0.81 | Neutral | 0.999 | Probably Damaging | 0.985 | Probably Damaging | 2.83 | Benign | 0.31 | Tolerated | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| c.352A>C | M118L 2D  AIThe SynGAP1 missense variant M118L is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect for M118L, and this conclusion does not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -1.319 | Likely Benign | 0.206 | Likely Benign | Likely Benign | 0.218 | Likely Benign | 0.1835 | 0.4511 | -1.09 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.11 | Benign | 0.03 | Affected | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.352A>G | M118V 2D  AIThe SynGAP1 missense variant M118V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -2.322 | Likely Benign | 0.122 | Likely Benign | Likely Benign | 0.158 | Likely Benign | 0.3326 | 0.3630 | -1.23 | Neutral | 0.012 | Benign | 0.011 | Benign | 3.98 | Benign | 0.02 | Affected | 2 | 1 | 2.3 | -32.06 | |||||||||||||||||||||||||||||||||||
| c.352A>T | M118L 2D AIThe SynGAP1 missense variant M118L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT indicates a pathogenic effect, while the SGM‑Consensus (majority vote from 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 (derived from the four 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 evidence points to a benign impact for M118L, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -1.319 | Likely Benign | 0.206 | Likely Benign | Likely Benign | 0.218 | Likely Benign | 0.1835 | 0.4511 | -1.09 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.11 | Benign | 0.03 | Affected | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.353T>A | M118K 2D  AIThe SynGAP1 missense variant M118K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for M118K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -3.979 | Likely Benign | 0.767 | Likely Pathogenic | Likely Benign | 0.276 | Likely Benign | 0.2010 | 0.1131 | -2.98 | Deleterious | 0.396 | Benign | 0.099 | Benign | 3.84 | Benign | 0.01 | Affected | 0 | -1 | -5.8 | -3.02 | ||||||||||||||||||||||||||||||||||||
| c.353T>C | M118T 2D  AIThe SynGAP1 missense variant M118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) also indicates a likely benign classification, and AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the evidence from multiple independent predictors and the high‑accuracy consensus strongly supports a benign impact. This conclusion is consistent with the lack of any ClinVar pathogenic annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -2.468 | Likely Benign | 0.454 | Ambiguous | Likely Benign | 0.217 | Likely Benign | 0.2207 | 0.2237 | -2.41 | Neutral | 0.396 | Benign | 0.067 | Benign | 3.86 | Benign | 0.08 | Tolerated | -1 | -1 | -2.6 | -30.09 | |||||||||||||||||||||||||||||||||||
| c.353T>G | M118R 2D  AIThe SynGAP1 missense variant M118R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact for M118R. This conclusion does not contradict any ClinVar annotation, as no ClinVar status is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -3.318 | Likely Benign | 0.698 | Likely Pathogenic | Likely Benign | 0.286 | Likely Benign | 0.2027 | 0.0913 | -3.17 | Deleterious | 0.697 | Possibly Damaging | 0.202 | Benign | 3.83 | Benign | 0.00 | Affected | 0 | -1 | -6.4 | 24.99 | ||||||||||||||||||||||||||||||||||||
| c.354G>A | M118I 2D  AIThe SynGAP1 missense variant M118I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -3.396 | Likely Benign | 0.754 | Likely Pathogenic | Likely Benign | 0.139 | Likely Benign | 0.1624 | 0.3570 | -1.23 | Neutral | 0.005 | Benign | 0.004 | Benign | 3.99 | Benign | 0.02 | Affected | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.354G>C | M118I 2D AIThe SynGAP1 missense variant M118I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -3.396 | Likely Benign | 0.754 | Likely Pathogenic | Likely Benign | 0.140 | Likely Benign | 0.1624 | 0.3570 | -1.23 | Neutral | 0.005 | Benign | 0.004 | Benign | 3.99 | Benign | 0.02 | Affected | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.354G>T | M118I 2D AIThe SynGAP1 missense variant M118I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.694846 | Disordered | 0.676867 | Binding | 0.330 | 0.883 | 0.500 | -3.396 | Likely Benign | 0.754 | Likely Pathogenic | Likely Benign | 0.139 | Likely Benign | 0.1624 | 0.3570 | -1.23 | Neutral | 0.005 | Benign | 0.004 | Benign | 3.99 | Benign | 0.02 | Affected | 2 | 1 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.370G>A | A124T 2D AIThe SynGAP1 missense variant A124T is reported in gnomAD (6-33432235‑G‑A) 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, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | 6-33432235-G-A | 1 | 6.20e-7 | -3.551 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.046 | Likely Benign | 0.1828 | 0.7680 | -0.26 | Neutral | 0.734 | Possibly Damaging | 0.187 | Benign | 4.17 | Benign | 0.78 | Tolerated | 3.61 | 5 | 0 | 1 | -2.5 | 30.03 | ||||||||||||||||||||||||||||||
| c.370G>C | A124P 2D AIThe SynGAP1 missense variant A124P is not reported 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 analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for A124P, 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 | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | -3.030 | Likely Benign | 0.092 | Likely Benign | Likely Benign | 0.134 | Likely Benign | 0.2293 | 0.6141 | -1.19 | Neutral | 0.984 | Probably Damaging | 0.690 | Possibly Damaging | 4.05 | Benign | 0.03 | Affected | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.370G>T | A124S 2D AIThe SynGAP1 missense variant A124 S 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 | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | -1.933 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.053 | Likely Benign | 0.3018 | 0.6192 | 0.35 | Neutral | 0.849 | Possibly Damaging | 0.303 | Benign | 4.22 | Benign | 0.65 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.371C>A | A124E 2D AIThe SynGAP1 missense variant A124E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A124E, 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 | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | -3.444 | Likely Benign | 0.667 | Likely Pathogenic | Likely Benign | 0.208 | Likely Benign | 0.1498 | 0.2233 | -1.21 | Neutral | 0.993 | Probably Damaging | 0.733 | Possibly Damaging | 4.11 | Benign | 0.01 | Affected | 0 | -1 | -5.3 | 58.04 | |||||||||||||||||||||||||||||||||||
| c.371C>G | A124G 2D AIThe SynGAP1 missense variant A124G 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 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 | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | -3.090 | Likely Benign | 0.164 | Likely Benign | Likely Benign | 0.055 | Likely Benign | 0.2433 | 0.5388 | -0.75 | Neutral | 0.934 | Possibly Damaging | 0.447 | Possibly Damaging | 4.06 | Benign | 0.04 | Affected | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.371C>T | A124V 2D AIThe SynGAP1 A124V missense variant is listed in ClinVar (ID 1040523.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33432236‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of computational evidence indicates a benign effect, and this consensus does not contradict the ClinVar “Uncertain” designation. 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 | 0.509769 | Disordered | 0.699139 | Binding | 0.340 | 0.883 | 0.750 | Conflicting | 2 | 6-33432236-C-T | 9 | 5.58e-6 | -4.259 | Likely Benign | 0.138 | Likely Benign | Likely Benign | 0.073 | Likely Benign | 0.1415 | 0.7433 | -1.52 | Neutral | 0.173 | Benign | 0.009 | Benign | 4.07 | Benign | 0.03 | Affected | 3.61 | 5 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||
| c.85A>C | M29L 2D AIThe SynGAP1 missense variant M29L is not reported 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 | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -1.633 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.200 | Likely Benign | 0.1984 | 0.5336 | -0.49 | Neutral | 0.006 | Benign | 0.039 | Benign | 4.27 | Benign | 0.00 | Affected | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.85A>G | M29V 2D AIThe SynGAP1 missense variant M29V is reported in gnomAD (ID 6‑33423494‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, representing the sole discordant signal. 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 M29V, 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 | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | 6-33423494-A-G | 1 | 6.20e-7 | -1.841 | Likely Benign | 0.057 | Likely Benign | Likely Benign | 0.209 | Likely Benign | 0.4022 | 0.4433 | -0.39 | Neutral | 0.006 | Benign | 0.091 | Benign | 4.27 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||||||||||
| c.85A>T | M29L 2D AIThe SynGAP1 missense variant M29L is not reported 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; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -1.633 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.200 | Likely Benign | 0.1984 | 0.5336 | -0.49 | Neutral | 0.006 | Benign | 0.039 | Benign | 4.27 | Benign | 0.00 | Affected | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.86T>A | M29K 2D AIThe SynGAP1 missense variant M29K is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency or clinical annotation. Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 a benign interpretation: 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 collective predictions point to a benign effect, and this conclusion does not contradict the absence of a ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -2.514 | Likely Benign | 0.287 | Likely Benign | Likely Benign | 0.197 | Likely Benign | 0.2019 | 0.1312 | -0.88 | Neutral | 0.018 | Benign | 0.184 | Benign | 4.27 | Benign | 0.00 | Affected | 0 | -1 | -5.8 | -3.02 | |||||||||||||||||||||||||||||||||||
| c.86T>C | M29T 2D AIThe SynGAP1 missense variant M29T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that M29T is most likely benign, 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 | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | Uncertain | 1 | -2.167 | Likely Benign | 0.122 | Likely Benign | Likely Benign | 0.199 | Likely Benign | 0.2633 | 0.2716 | -0.37 | Neutral | 0.018 | Benign | 0.184 | Benign | 4.33 | Benign | 0.00 | Affected | 4.32 | 1 | -1 | -1 | -2.6 | -30.09 | |||||||||||||||||||||||||||||||
| c.86T>G | M29R 2D AIThe SynGAP1 missense variant M29R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -1.708 | Likely Benign | 0.241 | Likely Benign | Likely Benign | 0.211 | Likely Benign | 0.2076 | 0.1293 | -0.92 | Neutral | 0.042 | Benign | 0.184 | Benign | 4.23 | Benign | 0.00 | Affected | 0 | -1 | -6.4 | 24.99 | |||||||||||||||||||||||||||||||||||
| c.87G>A | M29I 2D AIThe SynGAP1 missense variant M29I is catalogued in gnomAD (6-33423496‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta stability analysis is unavailable for this variant. Overall, the preponderance 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 | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | 6-33423496-G-A | 6 | 3.72e-6 | -2.425 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.067 | Likely Benign | 0.1680 | 0.4385 | -0.51 | Neutral | 0.006 | Benign | 0.091 | Benign | 4.26 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | 2.6 | -18.03 | ||||||||||||||||||||||||||||||
| c.87G>C | M29I 2D AIThe SynGAP1 missense variant M29I is not reported 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 not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -2.425 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.067 | Likely Benign | 0.1680 | 0.4385 | -0.51 | Neutral | 0.006 | Benign | 0.091 | Benign | 4.26 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||
| c.87G>T | M29I 2D AIThe SynGAP1 missense variant M29I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this assessment 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 | 0.541878 | Disordered | 0.438540 | Uncertain | 0.341 | 0.883 | 0.250 | -2.425 | Likely Benign | 0.185 | Likely Benign | Likely Benign | 0.067 | Likely Benign | 0.1680 | 0.4385 | -0.51 | Neutral | 0.006 | Benign | 0.091 | Benign | 4.26 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||
| c.88C>A | H30N 2D AIThe SynGAP1 missense variant H30N is not reported in ClinVar and is absent from gnomAD. Consensus among most in silico predictors is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect, while only SIFT predicts pathogenicity. Grouping the tools, the benign‑predicting set (nine tools) overwhelmingly outweighs the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -3.096 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.052 | Likely Benign | 0.2699 | 0.3818 | -1.91 | Neutral | 0.273 | Benign | 0.380 | Benign | 3.92 | Benign | 0.00 | Affected | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||
| c.88C>G | H30D 2D AIThe SynGAP1 missense variant H30D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for H30D, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -2.838 | Likely Benign | 0.318 | Likely Benign | Likely Benign | 0.150 | Likely Benign | 0.3048 | 0.3296 | -2.25 | Neutral | 0.462 | Possibly Damaging | 0.599 | Possibly Damaging | 3.93 | Benign | 0.00 | Affected | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||
| c.88C>T | H30Y 2D AIThe SynGAP1 H30Y missense variant (ClinVar ID 972248.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumVar and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | Uncertain | 1 | -3.047 | Likely Benign | 0.115 | Likely Benign | Likely Benign | 0.082 | Likely Benign | 0.1572 | 0.4856 | -1.84 | Neutral | 0.273 | Benign | 0.478 | Possibly Damaging | 3.99 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||
| c.89A>C | H30P 2D AIThe SynGAP1 H30P missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -1.933 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.202 | Likely Benign | 0.2527 | 0.4723 | -2.77 | Deleterious | 0.676 | Possibly Damaging | 0.599 | Possibly Damaging | 3.89 | Benign | 0.00 | Affected | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||
| c.89A>G | H30R 2D AIThe SynGAP1 missense variant H30R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -2.156 | Likely Benign | 0.186 | Likely Benign | Likely Benign | 0.138 | Likely Benign | 0.2762 | 0.3590 | -2.17 | Neutral | 0.462 | Possibly Damaging | 0.599 | Possibly Damaging | 3.94 | Benign | 0.00 | Affected | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||
| c.89A>T | H30L 2D AIThe SynGAP1 H30L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -2.073 | Likely Benign | 0.117 | Likely Benign | Likely Benign | 0.163 | Likely Benign | 0.1523 | 0.5793 | -2.88 | Deleterious | 0.462 | Possibly Damaging | 0.599 | Possibly Damaging | 3.94 | Benign | 0.00 | Affected | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||
| c.90C>A | H30Q 2D AIThe SynGAP1 H30Q missense change is catalogued in gnomAD (ID 6‑33423499‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: six methods (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all indicate a benign effect, while three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT) predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (derived from the four benign‑predicting tools) also yields a benign verdict. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with ClinVar, which currently contains no classification for H30Q. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | 6-33423499-C-A | 1 | 6.20e-7 | -3.016 | Likely Benign | 0.142 | Likely Benign | Likely Benign | 0.068 | Likely Benign | 0.2409 | 0.4422 | -2.21 | Neutral | 0.462 | Possibly Damaging | 0.599 | Possibly Damaging | 3.93 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 3 | -0.3 | -9.01 | ||||||||||||||||||||||||||||||
| c.90C>G | H30Q 2D AIThe SynGAP1 missense variant H30Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.570702 | Disordered | 0.438063 | Uncertain | 0.373 | 0.883 | 0.250 | -3.016 | Likely Benign | 0.142 | Likely Benign | Likely Benign | 0.068 | Likely Benign | 0.2409 | 0.4422 | -2.21 | Neutral | 0.462 | Possibly Damaging | 0.599 | Possibly Damaging | 3.93 | Benign | 0.00 | Affected | 4.32 | 1 | 0 | 3 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||
| c.1129A>C | M377L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377L is catalogued in gnomAD (ID 6‑33438034‑A‑C) but has no entry in ClinVar. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign. Only Rosetta yields an uncertain result, which is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, reports benign. No tool predicts pathogenicity. Consequently, the variant 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 | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | 6-33438034-A-C | 1 | 1.95e-6 | -2.394 | Likely Benign | 0.082 | Likely Benign | Likely Benign | 0.175 | Likely Benign | 0.2516 | 0.4885 | 0.13 | Likely Benign | 0.1 | 0.69 | Ambiguous | 0.41 | Likely Benign | 0.16 | Likely Benign | -0.32 | Neutral | 0.000 | Benign | 0.001 | Benign | 5.46 | Benign | 0.58 | Tolerated | 4.32 | 12 | 2 | 4 | 1.9 | -18.03 | ||||||||||||||||||||
| c.1129A>G | M377V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (gnomAD ID 6‑33438034‑A‑G). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from FoldX, Rosetta, and Foldetta, which are treated as unavailable. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, while Foldetta remains uncertain. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | 6-33438034-A-G | -1.507 | Likely Benign | 0.073 | Likely Benign | Likely Benign | 0.161 | Likely Benign | 0.4530 | 0.4096 | 0.92 | Ambiguous | 0.3 | 1.27 | Ambiguous | 1.10 | Ambiguous | 0.48 | Likely Benign | -0.31 | Neutral | 0.000 | Benign | 0.000 | Benign | 5.46 | Benign | 0.15 | Tolerated | 4.32 | 12 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||
| c.1129A>T | M377L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377L is reported in gnomAD (variant ID 6‑33438034‑A‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. No inconclusive or missing predictions are present. Based on the collective evidence, the variant is most likely benign, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | 6-33438034-A-T | -2.394 | Likely Benign | 0.082 | Likely Benign | Likely Benign | 0.186 | Likely Benign | 0.2516 | 0.4885 | 0.13 | Likely Benign | 0.1 | 0.69 | Ambiguous | 0.41 | Likely Benign | 0.16 | Likely Benign | -0.32 | Neutral | 0.000 | Benign | 0.001 | Benign | 5.46 | Benign | 0.58 | Tolerated | 4.32 | 12 | 2 | 4 | 1.9 | -18.03 | ||||||||||||||||||||||
| c.1130T>A | M377K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are Rosetta and Foldetta. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome, while premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | -3.718 | Likely Benign | 0.226 | Likely Benign | Likely Benign | 0.440 | Likely Benign | 0.2423 | 0.1671 | 0.20 | Likely Benign | 0.2 | 4.44 | Destabilizing | 2.32 | Destabilizing | 0.62 | Ambiguous | -0.26 | Neutral | 0.002 | Benign | 0.003 | Benign | 5.46 | Benign | 0.07 | Tolerated | 0 | -1 | -5.8 | -3.02 | |||||||||||||||||||||||||
| c.1130T>C | M377T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377T is reported in gnomAD (variant ID 6‑33438035‑T‑C) but has no ClinVar entry. Functional 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. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence points to a benign effect for M377T, 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 | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | 6-33438035-T-C | 5 | 1.17e-5 | -1.881 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.245 | Likely Benign | 0.3064 | 0.3267 | 0.90 | Ambiguous | 0.4 | 1.95 | Ambiguous | 1.43 | Ambiguous | 0.59 | Ambiguous | -0.65 | Neutral | 0.000 | Benign | 0.002 | Benign | 5.47 | Benign | 0.05 | Affected | 4.32 | 12 | -1 | -1 | -2.6 | -30.09 | ||||||||||||||||||||
| c.1130T>G | M377R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377R is present in gnomAD (6‑33438035‑T‑G) and has no ClinVar entry. Prediction tools that report a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are Rosetta and Foldetta. The high‑accuracy consensus (SGM‑Consensus) is “Likely Benign,” derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—all of which are benign. AlphaMissense‑Optimized also predicts benign, whereas Foldetta predicts pathogenic. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status (which is currently absent). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | 6-33438035-T-G | -3.150 | Likely Benign | 0.219 | Likely Benign | Likely Benign | 0.471 | Likely Benign | 0.2369 | 0.1918 | 0.49 | Likely Benign | 0.4 | 4.81 | Destabilizing | 2.65 | Destabilizing | 0.69 | Ambiguous | -0.64 | Neutral | 0.004 | Benign | 0.009 | Benign | 5.46 | Benign | 0.18 | Tolerated | 4.32 | 12 | -1 | 0 | -6.4 | 24.99 | ||||||||||||||||||||||
| c.1131G>A | M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I (ClinVar ID 3803473.0, status = Uncertain) is present in gnomAD (ID = 6‑33438036‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the computational evidence strongly favors a benign classification, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | Uncertain | 1 | 6-33438036-G-A | 1 | 6.23e-7 | -2.895 | Likely Benign | 0.212 | Likely Benign | Likely Benign | 0.227 | Likely Benign | 0.2240 | 0.4133 | 0.76 | Ambiguous | 0.3 | 0.54 | Ambiguous | 0.65 | Ambiguous | 0.24 | Likely Benign | -0.41 | Neutral | 0.000 | Benign | 0.001 | Benign | 5.46 | Benign | 0.26 | Tolerated | 4.32 | 12 | 1 | 2 | 2.6 | -18.03 | ||||||||||||||||||
| c.1131G>C | M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. Overall, the collective evidence points to a benign impact for M377I, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | -2.895 | Likely Benign | 0.212 | Likely Benign | Likely Benign | 0.227 | Likely Benign | 0.2240 | 0.4133 | 0.76 | Ambiguous | 0.3 | 0.54 | Ambiguous | 0.65 | Ambiguous | 0.24 | Likely Benign | -0.41 | Neutral | 0.000 | Benign | 0.001 | Benign | 5.46 | Benign | 0.26 | Tolerated | 4.32 | 12 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||
| c.1131G>T | M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. Overall, the evidence overwhelmingly supports a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | C2 | 0.675549 | Disordered | 0.431183 | Uncertain | 0.324 | 0.884 | 0.625 | -2.895 | Likely Benign | 0.212 | Likely Benign | Likely Benign | 0.227 | Likely Benign | 0.2240 | 0.4133 | 0.76 | Ambiguous | 0.3 | 0.54 | Ambiguous | 0.65 | Ambiguous | 0.24 | Likely Benign | -0.41 | Neutral | 0.000 | Benign | 0.001 | Benign | 5.46 | Benign | 0.26 | Tolerated | 4.32 | 12 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||
| c.2314T>A | F772I 2D AIThe SynGAP1 missense variant F772I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -2.925 | Likely Benign | 0.255 | Likely Benign | Likely Benign | 0.142 | Likely Benign | 0.1544 | 0.2051 | -0.38 | Neutral | 0.845 | Possibly Damaging | 0.899 | Possibly Damaging | 4.24 | Benign | 0.41 | Tolerated | 1 | 0 | 1.7 | -34.02 | |||||||||||||||||||||||||||||||||||
| c.2314T>C | F772L 2D AIThe SynGAP1 missense variant F772L is listed in gnomAD (6‑33442472‑T‑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 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, 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 absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | 6-33442472-T-C | 1 | 1.28e-6 | -1.751 | Likely Benign | 0.762 | Likely Pathogenic | Likely Benign | 0.161 | Likely Benign | 0.1661 | 0.3033 | -0.47 | Neutral | 0.508 | Possibly Damaging | 0.786 | Possibly Damaging | 4.31 | Benign | 1.00 | Tolerated | 3.64 | 6 | 0 | 2 | 1.0 | -34.02 | ||||||||||||||||||||||||||||||
| c.2314T>G | F772V 2D AIThe SynGAP1 missense variant F772V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are not available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -2.886 | Likely Benign | 0.191 | Likely Benign | Likely Benign | 0.161 | Likely Benign | 0.1687 | 0.2419 | -0.43 | Neutral | 0.845 | Possibly Damaging | 0.899 | Possibly Damaging | 4.27 | Benign | 0.37 | Tolerated | -1 | -1 | 1.4 | -48.04 | |||||||||||||||||||||||||||||||||||
| c.2315T>A | F772Y 2D AIThe SynGAP1 missense variant F772Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -2.657 | Likely Benign | 0.117 | Likely Benign | Likely Benign | 0.114 | Likely Benign | 0.1058 | 0.1892 | -0.54 | Neutral | 0.705 | Possibly Damaging | 0.786 | Possibly Damaging | 4.17 | Benign | 0.35 | Tolerated | 7 | 3 | -4.1 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.2315T>C | F772S 2D AIThe SynGAP1 missense variant F772S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus likewise indicates Likely Benign; Foldetta data are not available. Overall, the preponderance of evidence points to a benign effect for F772S, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -2.722 | Likely Benign | 0.442 | Ambiguous | Likely Benign | 0.138 | Likely Benign | 0.4134 | 0.0558 | -0.26 | Neutral | 0.845 | Possibly Damaging | 0.899 | Possibly Damaging | 4.21 | Benign | 0.56 | Tolerated | -3 | -2 | -3.6 | -60.10 | |||||||||||||||||||||||||||||||||||
| c.2315T>G | F772C 2D AIThe SynGAP1 missense variant F772C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -4.498 | Likely Benign | 0.248 | Likely Benign | Likely Benign | 0.156 | Likely Benign | 0.2450 | 0.1419 | -1.46 | Neutral | 0.979 | Probably Damaging | 0.985 | Probably Damaging | 4.14 | Benign | 0.10 | Tolerated | -4 | -2 | -0.3 | -44.04 | |||||||||||||||||||||||||||||||||||
| c.2316C>A | F772L 2D AIThe SynGAP1 missense variant F772L is catalogued in gnomAD (ID 6‑33442474‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from 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 outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the preponderance of evidence indicates that F772L 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 | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | 6-33442474-C-A | -1.751 | Likely Benign | 0.762 | Likely Pathogenic | Likely Benign | 0.109 | Likely Benign | 0.1661 | 0.3033 | -0.47 | Neutral | 0.508 | Possibly Damaging | 0.786 | Possibly Damaging | 4.31 | Benign | 1.00 | Tolerated | 3.64 | 6 | 0 | 2 | 1.0 | -34.02 | ||||||||||||||||||||||||||||||||
| c.2316C>G | F772L 2D AIThe SynGAP1 missense variant F772L has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability data are available, so it is treated as unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.450668 | Structured | 0.922662 | Binding | 0.329 | 0.884 | 0.250 | -1.751 | Likely Benign | 0.762 | Likely Pathogenic | Likely Benign | 0.109 | Likely Benign | 0.1661 | 0.3033 | -0.47 | Neutral | 0.508 | Possibly Damaging | 0.786 | Possibly Damaging | 4.31 | Benign | 1.00 | Tolerated | 3.64 | 6 | 0 | 2 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||
| c.2398G>A | G800S 2D AIThe SynGAP1 missense variant G800S is reported as “Likely Benign” by the SGM‑Consensus method and is absent from ClinVar and gnomAD. All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | -3.572 | Likely Benign | 0.088 | Likely Benign | Likely Benign | 0.083 | Likely Benign | 0.2375 | 0.4923 | -0.69 | Neutral | 0.292 | Benign | 0.157 | Benign | 2.78 | Benign | 0.60 | Tolerated | 1 | 0 | -0.4 | 30.03 | ||||||||||||||||||||||||||||||||||
| c.2398G>C | G800R 2D AIThe SynGAP1 missense variant G800R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | -3.613 | Likely Benign | 0.405 | Ambiguous | Likely Benign | 0.147 | Likely Benign | 0.0868 | 0.3835 | -0.27 | Neutral | 0.003 | Benign | 0.004 | Benign | 2.84 | Benign | 0.17 | Tolerated | -3 | -2 | -4.1 | 99.14 | ||||||||||||||||||||||||||||||||||
| c.2398G>T | G800C 2D AIThe SynGAP1 missense variant G800C is not reported in ClinVar and has no allele in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of a ClinVar pathogenic annotation. Based on the aggregate predictions, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | -7.074 | In-Between | 0.129 | Likely Benign | Likely Benign | 0.144 | Likely Benign | 0.1102 | 0.4189 | -1.53 | Neutral | 0.994 | Probably Damaging | 0.840 | Possibly Damaging | 2.70 | Benign | 0.15 | Tolerated | -3 | -3 | 2.9 | 46.09 | ||||||||||||||||||||||||||||||||||
| c.2399G>A | G800D 2D AIThe SynGAP1 missense variant G800D is catalogued in gnomAD (6-33442951‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (derived from the majority of the four high‑accuracy predictors) also yields a benign verdict. Foldetta results are unavailable, so they do not influence the assessment. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | 6-33442951-G-A | -5.929 | Likely Benign | 0.400 | Ambiguous | Likely Benign | 0.088 | Likely Benign | 0.1664 | 0.1877 | -0.84 | Neutral | 0.451 | Benign | 0.265 | Benign | 2.76 | Benign | 0.34 | Tolerated | 4.32 | 2 | -1 | 1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||
| c.2399G>C | G800A 2D AIThe SynGAP1 missense variant G800A is listed in gnomAD (6-33442951‑G‑C) but has no ClinVar entry. Across the available in‑silico predictors, every tool reports a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant. Based on the unanimous benign predictions and the absence of any pathogenic calls, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | 6-33442951-G-C | 7 | 4.34e-6 | -3.550 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.031 | Likely Benign | 0.3466 | 0.4850 | -0.48 | Neutral | 0.011 | Benign | 0.006 | Benign | 2.78 | Benign | 1.00 | Tolerated | 4.32 | 2 | 0 | 1 | 2.2 | 14.03 | 10.1016/j.ajhg.2020.11.011 | ||||||||||||||||||||||||||||
| c.2399G>T | G800V 2D AIThe SynGAP1 missense variant G800V is predicted to be benign by all evaluated in‑silico tools. ClinVar contains no entry for this variant, and it is not reported in gnomAD. Consensus predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | SH3-binding motif | 0.852992 | Disordered | 0.588350 | Binding | 0.303 | 0.884 | 0.625 | -4.890 | Likely Benign | 0.113 | Likely Benign | Likely Benign | 0.078 | Likely Benign | 0.1130 | 0.4198 | -1.24 | Neutral | 0.451 | Benign | 0.157 | Benign | 2.73 | Benign | 0.25 | Tolerated | -1 | -3 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||||
| c.2467A>C | S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools points to a pathogenic effect for S823R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.612 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.293 | Likely Benign | 0.0893 | 0.4046 | -3.47 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.93 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2467A>G | S823G 2D AIThe SynGAP1 missense variant S823G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the Foldetta stability analysis is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.034 | Likely Benign | 0.822 | Likely Pathogenic | Ambiguous | 0.202 | Likely Benign | 0.2855 | 0.5287 | -2.59 | Deleterious | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 1.96 | Pathogenic | 0.00 | Affected | 1 | 0 | 0.4 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.2467A>T | S823C 2D AIThe SynGAP1 missense variant S823C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability prediction is available, so it does not contribute to the assessment. Overall, the preponderance of evidence points to a pathogenic effect for S823C, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -7.881 | In-Between | 0.911 | Likely Pathogenic | Ambiguous | 0.332 | Likely Benign | 0.1019 | 0.6137 | -3.80 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 1.91 | Pathogenic | 0.00 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2468G>A | S823N 2D AIThe SynGAP1 missense variant S823N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.880 | Likely Benign | 0.974 | Likely Pathogenic | Likely Pathogenic | 0.170 | Likely Benign | 0.1370 | 0.5172 | -1.76 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 1.93 | Pathogenic | 0.00 | Affected | 1 | 1 | -2.7 | 27.03 | ||||||||||||||||||||||||||||||||||||
| c.2468G>C | S823T 2D AIThe SynGAP1 missense variant S823T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two benign, two pathogenic). AlphaMissense‑Optimized predicts benign, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.036 | Likely Benign | 0.717 | Likely Pathogenic | Likely Benign | 0.165 | Likely Benign | 0.1453 | 0.6580 | -2.02 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.05 | Pathogenic | 0.00 | Affected | 1 | 1 | 0.1 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2468G>T | S823I 2D AIThe SynGAP1 missense variant S823I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only REVEL predicts a benign outcome, while ESM1b remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -7.332 | In-Between | 0.990 | Likely Pathogenic | Likely Pathogenic | 0.287 | Likely Benign | 0.0964 | 0.5848 | -4.26 | Deleterious | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 1.92 | Pathogenic | 0.00 | Affected | -1 | -2 | 5.3 | 26.08 | |||||||||||||||||||||||||||||||||||
| c.2469C>A | S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.612 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.196 | Likely Benign | 0.0893 | 0.4046 | -3.47 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.93 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2469C>G | S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.685117 | Disordered | 0.627336 | Binding | 0.358 | 0.884 | 0.750 | -6.612 | Likely Benign | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.196 | Likely Benign | 0.0893 | 0.4046 | -3.47 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.93 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2470A>C | S824R 2D AIThe SynGAP1 missense variant S824R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign interpretation, but the split in high‑accuracy tools introduces uncertainty. The variant is therefore most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -5.589 | Likely Benign | 0.996 | Likely Pathogenic | Likely Pathogenic | 0.131 | Likely Benign | 0.1096 | 0.4255 | -1.67 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.61 | Benign | 0.23 | Tolerated | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2470A>G | S824G 2D AIThe SynGAP1 missense variant S824G is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443022‑A‑G). 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. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Based on the preponderance of benign predictions and the consensus from high‑accuracy tools, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | 6-33443022-A-G | 1 | 6.20e-7 | -5.476 | Likely Benign | 0.543 | Ambiguous | Likely Benign | 0.079 | Likely Benign | 0.2880 | 0.5437 | -1.74 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.60 | Benign | 0.50 | Tolerated | 3.77 | 5 | 0 | 1 | 0.4 | -30.03 | ||||||||||||||||||||||||||||||
| c.2470A>T | S824C 2D AIThe SynGAP1 missense variant S824C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S824C, 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 | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -6.613 | Likely Benign | 0.730 | Likely Pathogenic | Likely Benign | 0.108 | Likely Benign | 0.1363 | 0.6277 | -1.87 | Neutral | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.57 | Benign | 0.07 | Tolerated | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2471G>A | S824N 2D AIThe SynGAP1 missense variant S824N is reported in gnomAD (6‑33443023‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic impact 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, 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 | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | 6-33443023-G-A | 2 | 1.24e-6 | -4.473 | Likely Benign | 0.909 | Likely Pathogenic | Ambiguous | 0.091 | Likely Benign | 0.1713 | 0.5327 | -1.08 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.67 | Benign | 0.61 | Tolerated | 3.77 | 5 | 1 | 1 | -2.7 | 27.03 | ||||||||||||||||||||||||||||||
| c.2471G>C | S824T 2D AIThe SynGAP1 missense variant S824T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -4.135 | Likely Benign | 0.500 | Ambiguous | Likely Benign | 0.116 | Likely Benign | 0.1760 | 0.6525 | -0.74 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.62 | Benign | 0.47 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2471G>T | S824I 2D AIThe SynGAP1 missense variant S824I has no ClinVar record and is not listed in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the balance of evidence—five benign versus three pathogenic calls, a benign SGM‑Consensus, and no conflicting ClinVar annotation—suggests that the variant is most likely benign. This conclusion does not contradict any existing ClinVar status, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -6.799 | Likely Benign | 0.950 | Likely Pathogenic | Ambiguous | 0.124 | Likely Benign | 0.1177 | 0.6045 | -1.18 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.60 | Benign | 0.11 | Tolerated | -1 | -2 | 5.3 | 26.08 | |||||||||||||||||||||||||||||||||||
| c.2472C>A | S824R 2D AIThe SynGAP1 missense variant S824R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of tools lean toward a benign interpretation, but the presence of a pathogenic prediction from a high‑accuracy model introduces uncertainty. Thus, the variant is most likely benign based on the current predictions, and this assessment does not contradict the ClinVar status, which has no reported classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -5.589 | Likely Benign | 0.996 | Likely Pathogenic | Likely Pathogenic | 0.154 | Likely Benign | 0.1096 | 0.4255 | -1.67 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.61 | Benign | 0.23 | Tolerated | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2472C>G | S824R 2D AIThe SynGAP1 missense variant S824R is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus score, which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) is benign; Foldetta, a protein‑folding stability predictor, 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, as none exists for S824R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.611272 | Binding | 0.314 | 0.884 | 0.750 | -5.589 | Likely Benign | 0.996 | Likely Pathogenic | Likely Pathogenic | 0.154 | Likely Benign | 0.1096 | 0.4255 | -1.67 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.61 | Benign | 0.23 | Tolerated | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2479A>C | I827L 2D AIThe SynGAP1 missense variant I827L is not reported 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 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 | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -2.535 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.120 | Likely Benign | 0.0711 | 0.2901 | -0.64 | Neutral | 0.981 | Probably Damaging | 0.970 | Probably Damaging | 2.71 | Benign | 0.43 | Tolerated | 2 | 2 | -0.7 | 0.00 | |||||||||||||||||||||||||||||||||||
| c.2479A>G | I827V 2D AIThe SynGAP1 missense variant I827V is not reported 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 the I827V 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 | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -3.590 | Likely Benign | 0.249 | Likely Benign | Likely Benign | 0.129 | Likely Benign | 0.1011 | 0.2536 | 0.05 | Neutral | 0.958 | Probably Damaging | 0.970 | Probably Damaging | 2.70 | Benign | 1.00 | Tolerated | 4 | 3 | -0.3 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2479A>T | I827F 2D AIThe SynGAP1 missense variant I827F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -4.799 | Likely Benign | 0.517 | Ambiguous | Likely Benign | 0.155 | Likely Benign | 0.0490 | 0.2306 | -1.30 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.65 | Benign | 0.09 | Tolerated | 1 | 0 | -1.7 | 34.02 | |||||||||||||||||||||||||||||||||||
| c.2480T>A | I827N 2D AIThe SynGAP1 missense variant I827N 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, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the preponderance of evidence points to a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -4.860 | Likely Benign | 0.804 | Likely Pathogenic | Ambiguous | 0.114 | Likely Benign | 0.0876 | 0.0342 | -1.69 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.66 | Benign | 0.11 | Tolerated | -2 | -3 | -8.0 | 0.94 | |||||||||||||||||||||||||||||||||||
| c.2480T>C | I827T 2D AIThe SynGAP1 missense variant I827T is not reported 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. 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 | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -4.586 | Likely Benign | 0.874 | Likely Pathogenic | Ambiguous | 0.147 | Likely Benign | 0.1002 | 0.0685 | -0.47 | Neutral | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.74 | Benign | 0.40 | Tolerated | 0 | -1 | -5.2 | -12.05 | |||||||||||||||||||||||||||||||||||
| c.2480T>G | I827S 2D AIThe SynGAP1 missense variant I827S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is classified as Uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -3.693 | Likely Benign | 0.849 | Likely Pathogenic | Ambiguous | 0.140 | Likely Benign | 0.2891 | 0.0512 | -0.42 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.70 | Benign | 0.29 | Tolerated | -1 | -2 | -5.3 | -26.08 | |||||||||||||||||||||||||||||||||||
| c.2481C>G | I827M 2D AIThe SynGAP1 missense variant I827M is not reported 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 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 | 0.590140 | Disordered | 0.636272 | Binding | 0.383 | 0.884 | 0.625 | -4.910 | Likely Benign | 0.282 | Likely Benign | Likely Benign | 0.143 | Likely Benign | 0.0642 | 0.2560 | -0.61 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.65 | Benign | 0.13 | Tolerated | 2 | 1 | -2.6 | 18.03 | |||||||||||||||||||||||||||||||||||
| 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 | 0.2155 | 0.6185 | -0.84 | Neutral | 0.965 | Probably Damaging | 0.782 | Possibly Damaging | 4.00 | Benign | 0.02 | Affected | 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 | 0.2405 | 0.5212 | -1.12 | Neutral | 0.990 | Probably Damaging | 0.892 | Possibly Damaging | 3.94 | Benign | 0.02 | Affected | 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 | 0.2820 | 0.5373 | -0.38 | Neutral | 0.965 | Probably Damaging | 0.702 | Possibly Damaging | 4.02 | Benign | 0.45 | Tolerated | 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 | 0.2253 | 0.2651 | -1.15 | Neutral | 0.990 | Probably Damaging | 0.892 | Possibly Damaging | 3.96 | Benign | 0.01 | Affected | 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 | 0.2180 | 0.4408 | -0.79 | Neutral | 0.965 | Probably Damaging | 0.702 | Possibly Damaging | 4.03 | Benign | 0.05 | Affected | 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 | 0.1966 | 0.5727 | -1.15 | Neutral | 0.818 | Possibly Damaging | 0.457 | Possibly Damaging | 4.01 | Benign | 0.01 | Affected | 0 | 0 | 2.4 | 28.05 | |||||||||||||||||||||||||||||||||||
| c.301C>A | H101N 2D AIThe SynGAP1 missense variant H101N 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 a majority vote of the benign‑predicted tools). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (derived from the same set of benign‑predicted tools) also indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -3.598 | Likely Benign | 0.072 | Likely Benign | Likely Benign | 0.104 | Likely Benign | 0.1651 | 0.2994 | -0.49 | Neutral | 0.659 | Possibly Damaging | 0.775 | Possibly Damaging | 4.20 | Benign | 0.00 | Affected | 2 | 1 | -0.3 | -23.04 | |||||||||||||||||||||||||||||||||||
| c.301C>G | H101D 2D AIThe SynGAP1 missense variant H101D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized 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 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 | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -2.788 | Likely Benign | 0.227 | Likely Benign | Likely Benign | 0.136 | Likely Benign | 0.2479 | 0.2272 | -0.49 | Neutral | 0.824 | Possibly Damaging | 0.840 | Possibly Damaging | 4.20 | Benign | 0.00 | Affected | 1 | -1 | -0.3 | -22.05 | |||||||||||||||||||||||||||||||||||
| c.301C>T | H101Y 2D AIThe SynGAP1 missense variant H101Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for H101Y, 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 | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -3.404 | Likely Benign | 0.123 | Likely Benign | Likely Benign | 0.099 | Likely Benign | 0.0862 | 0.4004 | -0.95 | Neutral | 0.659 | Possibly Damaging | 0.775 | Possibly Damaging | 4.15 | Benign | 0.00 | Affected | 0 | 2 | 1.9 | 26.03 | |||||||||||||||||||||||||||||||||||
| c.302A>C | H101P 2D AIThe SynGAP1 H101P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -2.042 | Likely Benign | 0.069 | Likely Benign | Likely Benign | 0.170 | Likely Benign | 0.1777 | 0.3589 | 0.89 | Neutral | 0.943 | Possibly Damaging | 0.924 | Probably Damaging | 4.17 | Benign | 0.00 | Affected | 0 | -2 | 1.6 | -40.02 | |||||||||||||||||||||||||||||||||||
| c.302A>G | H101R 2D AIThe SynGAP1 missense variant H101R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for H101R, 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 | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -2.685 | Likely Benign | 0.211 | Likely Benign | Likely Benign | 0.141 | Likely Benign | 0.1891 | 0.2225 | -0.76 | Neutral | 0.824 | Possibly Damaging | 0.840 | Possibly Damaging | 4.21 | Benign | 0.00 | Affected | 2 | 0 | -1.3 | 19.05 | |||||||||||||||||||||||||||||||||||
| c.302A>T | H101L 2D AIThe SynGAP1 missense variant H101L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for H101L, 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 | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -1.376 | Likely Benign | 0.101 | Likely Benign | Likely Benign | 0.129 | Likely Benign | 0.0924 | 0.4960 | -1.33 | Neutral | 0.824 | Possibly Damaging | 0.840 | Possibly Damaging | 4.19 | Benign | 0.00 | Affected | -2 | -3 | 7.0 | -23.98 | |||||||||||||||||||||||||||||||||||
| c.303C>A | H101Q 2D AIThe SynGAP1 missense variant H101Q is listed in ClinVar with an uncertain significance (ClinVar ID 1307533.0) and is present in gnomAD (ID 6‑33432168‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, 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 majority of evidence points to a benign impact, and this is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | Uncertain | 1 | 6-33432168-C-A | 1 | 6.20e-7 | -2.827 | Likely Benign | 0.124 | Likely Benign | Likely Benign | 0.147 | Likely Benign | 0.1487 | 0.3689 | -0.37 | Neutral | 0.824 | Possibly Damaging | 0.880 | Possibly Damaging | 4.24 | Benign | 0.00 | Affected | 4.32 | 1 | 3 | 0 | -0.3 | -9.01 | ||||||||||||||||||||||||||||
| c.303C>G | H101Q 2D AIThe SynGAP1 missense variant H101Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for H101Q, 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 | 0.791621 | Disordered | 0.688356 | Binding | 0.370 | 0.884 | 0.625 | -2.827 | Likely Benign | 0.124 | Likely Benign | Likely Benign | 0.149 | Likely Benign | 0.1487 | 0.3689 | -0.37 | Neutral | 0.824 | Possibly Damaging | 0.880 | Possibly Damaging | 4.24 | Benign | 0.00 | Affected | 4.32 | 1 | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||
| c.3406C>A | Q1136K 2D AIThe SynGAP1 missense variant Q1136K is listed in gnomAD (ID 6‑33443958‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: 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 reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | 6-33443958-C-A | -5.698 | Likely Benign | 0.397 | Ambiguous | Likely Benign | 0.236 | Likely Benign | 0.1891 | 0.4841 | -1.43 | Neutral | 0.625 | Possibly Damaging | 0.258 | Benign | 5.55 | Benign | 0.17 | Tolerated | 4.32 | 2 | 1 | 1 | -0.4 | 0.04 | ||||||||||||||||||||||||||||||||
| c.3406C>G | Q1136E 2D AIThe SynGAP1 missense variant Q1136E is catalogued in gnomAD (ID 6‑33443958‑C‑G) and has no ClinVar entry. All evaluated in silico predictors uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely pathogenic outcome. 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, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | 6-33443958-C-G | 4 | 2.71e-6 | -6.677 | Likely Benign | 0.277 | Likely Benign | Likely Benign | 0.209 | Likely Benign | 0.1487 | 0.2886 | -1.13 | Neutral | 0.022 | Benign | 0.026 | Benign | 5.46 | Benign | 0.11 | Tolerated | 4.32 | 2 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||
| c.3407A>C | Q1136P 2D AIThe SynGAP1 missense variant Q1136P 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 Q1136P, 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 | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | -5.067 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.364 | Likely Benign | 0.2188 | 0.5344 | -1.06 | Neutral | 0.961 | Probably Damaging | 0.745 | Possibly Damaging | 5.42 | Benign | 0.03 | Affected | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.3407A>G | Q1136R 2D AIThe SynGAP1 missense variant Q1136R 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‑vote SGM‑Consensus also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also leans benign; Foldetta data are not available. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign classification, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | -5.526 | Likely Benign | 0.478 | Ambiguous | Likely Benign | 0.173 | Likely Benign | 0.1527 | 0.3073 | -1.42 | Neutral | 0.801 | Possibly Damaging | 0.506 | Possibly Damaging | 6.28 | Benign | 0.09 | Tolerated | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.3407A>T | Q1136L 2D AIThe SynGAP1 missense variant Q1136L 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 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 is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | -6.020 | Likely Benign | 0.203 | Likely Benign | Likely Benign | 0.242 | Likely Benign | 0.0861 | 0.6395 | -2.42 | Neutral | 0.005 | Benign | 0.026 | Benign | 5.44 | Benign | 0.23 | Tolerated | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.3408G>C | Q1136H 2D AIThe SynGAP1 missense variant Q1136H is not reported 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 likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1136H, 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 | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | -5.658 | Likely Benign | 0.305 | Likely Benign | Likely Benign | 0.347 | Likely Benign | 0.1482 | 0.4637 | -1.98 | Neutral | 0.989 | Probably Damaging | 0.879 | Possibly Damaging | 5.42 | Benign | 0.03 | Affected | 4.32 | 2 | 0 | 3 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||
| c.3408G>T | Q1136H 2D AIThe SynGAP1 missense variant Q1136H is reported in gnomAD (variant ID 6-33443960‑G‑T) 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, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus itself is Benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.903857 | Disordered | 0.775584 | Binding | 0.321 | 0.884 | 0.875 | 6-33443960-G-T | -5.658 | Likely Benign | 0.305 | Likely Benign | Likely Benign | 0.347 | Likely Benign | 0.1482 | 0.4637 | -1.98 | Neutral | 0.989 | Probably Damaging | 0.879 | Possibly Damaging | 5.42 | Benign | 0.03 | Affected | 4.32 | 2 | 0 | 3 | 0.3 | 9.01 | ||||||||||||||||||||||||||||||||
| c.82T>A | S28T 2D AIThe SynGAP1 missense variant S28T 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 any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | -3.810 | Likely Benign | 0.081 | Likely Benign | Likely Benign | 0.054 | Likely Benign | 0.1874 | 0.6140 | -0.21 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.20 | Benign | 0.64 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.82T>C | S28P 2D AIThe SynGAP1 missense variant S28P is listed in ClinVar (ID 1500161.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Overall, the collective evidence points to a benign classification for S28P, 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 | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | Uncertain | 1 | -3.309 | Likely Benign | 0.051 | Likely Benign | Likely Benign | 0.047 | Likely Benign | 0.2432 | 0.5499 | 1.37 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.53 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||
| c.82T>G | S28A 2D AIThe SynGAP1 missense variant S28A 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 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 | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | -3.517 | Likely Benign | 0.063 | Likely Benign | Likely Benign | 0.039 | Likely Benign | 0.5194 | 0.4958 | Weaken | 0.09 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.27 | Benign | 1.00 | Tolerated | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||
| c.83C>A | S28Y 2D AIThe SynGAP1 missense variant S28Y is not reported 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 unavailable. Overall, the majority of evidence points to a benign effect. There is no conflict with 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 | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | -4.521 | Likely Benign | 0.270 | Likely Benign | Likely Benign | 0.041 | Likely Benign | 0.0895 | 0.5067 | -0.94 | Neutral | 0.009 | Benign | 0.001 | Benign | 4.13 | Benign | 0.05 | Affected | -3 | -2 | -0.5 | 76.10 | |||||||||||||||||||||||||||||||||||
| c.83C>G | S28C 2D AIThe SynGAP1 missense variant S28C 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 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 | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | -4.800 | Likely Benign | 0.107 | Likely Benign | Likely Benign | 0.021 | Likely Benign | 0.1387 | 0.5741 | -0.26 | Neutral | 0.022 | Benign | 0.004 | Benign | 4.13 | Benign | 0.11 | Tolerated | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.83C>T | S28F 2D AIThe SynGAP1 missense variant S28F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.545602 | Disordered | 0.438157 | Uncertain | 0.354 | 0.884 | 0.125 | -4.548 | Likely Benign | 0.255 | Likely Benign | Likely Benign | 0.045 | Likely Benign | 0.0748 | 0.5340 | -1.13 | Neutral | 0.009 | Benign | 0.002 | Benign | 4.13 | Benign | 0.05 | Affected | -3 | -2 | 3.6 | 60.10 | |||||||||||||||||||||||||||||||||||
| c.3025G>A | E1009K 2D AIThe SynGAP1 missense variant E1009K is not 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 consensus tools (five pathogenic vs. three benign) indicate a pathogenic effect. 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. | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | -3.419 | Likely Benign | 0.897 | Likely Pathogenic | Ambiguous | 0.061 | Likely Benign | 0.2511 | 0.7625 | -1.90 | Neutral | 0.961 | Probably Damaging | 0.630 | Possibly Damaging | 2.41 | Pathogenic | 0.01 | Affected | 0 | 1 | -0.4 | -0.94 | ||||||||||||||||||||||||||||||||||||
| c.3025G>C | E1009Q 2D AIThe SynGAP1 missense variant E1009Q is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33443577‑G‑C). 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 aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward pathogenicity. Thus, the variant is most likely pathogenic based on 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. | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | 6-33443577-G-C | 1 | 6.20e-7 | -3.423 | Likely Benign | 0.615 | Likely Pathogenic | Likely Benign | 0.057 | Likely Benign | 0.1577 | 0.7242 | -1.65 | Neutral | 0.980 | Probably Damaging | 0.782 | Possibly Damaging | 2.39 | Pathogenic | 0.02 | Affected | 3.77 | 5 | 2 | 2 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||
| c.3026A>C | E1009A 2D AIThe SynGAP1 missense variant E1009A is listed in ClinVar (ID 2238288.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Overall, the majority of predictions (six pathogenic vs. three benign) lean toward a pathogenic impact, 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 Pathogenic | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | Uncertain | 1 | -3.118 | Likely Benign | 0.679 | Likely Pathogenic | Likely Benign | 0.109 | Likely Benign | 0.3959 | 0.7153 | -3.06 | Deleterious | 0.980 | Probably Damaging | 0.630 | Possibly Damaging | 2.39 | Pathogenic | 0.01 | Affected | 3.77 | 5 | 0 | -1 | 5.3 | -58.04 | |||||||||||||||||||||||||||||||
| c.3026A>G | E1009G 2D AIThe SynGAP1 missense variant E1009G is not 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. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | -2.758 | Likely Benign | 0.610 | Likely Pathogenic | Likely Benign | 0.123 | Likely Benign | 0.2800 | 0.6003 | -3.06 | Deleterious | 0.961 | Probably Damaging | 0.721 | Possibly Damaging | 2.36 | Pathogenic | 0.01 | Affected | 0 | -2 | 3.1 | -72.06 | |||||||||||||||||||||||||||||||||||
| c.3026A>T | E1009V 2D AIThe SynGAP1 missense variant E1009V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (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, PROVEAN), and no available data from Foldetta. Overall, the majority of evidence points to a deleterious effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | -3.660 | Likely Benign | 0.815 | Likely Pathogenic | Ambiguous | 0.156 | Likely Benign | 0.1111 | 0.7580 | -3.81 | Deleterious | 0.998 | Probably Damaging | 0.924 | Probably Damaging | 2.34 | Pathogenic | 0.00 | Affected | -2 | -2 | 7.7 | -29.98 | |||||||||||||||||||||||||||||||||||
| c.3027G>C | E1009D 2D AIThe SynGAP1 missense variant E1009D is reported in gnomAD (ID 6‑33443579‑G‑C) but has no ClinVar entry. All in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized indicates 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 effect, 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 | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | 6-33443579-G-C | 1 | 6.20e-7 | -2.958 | Likely Benign | 0.104 | Likely Benign | Likely Benign | 0.054 | Likely Benign | 0.2077 | 0.4817 | -0.37 | Neutral | 0.011 | Benign | 0.017 | Benign | 2.50 | Benign | 0.30 | Tolerated | 3.77 | 5 | 2 | 3 | 0.0 | -14.03 | ||||||||||||||||||||||||||||||
| c.3027G>T | E1009D 2D AIThe SynGAP1 missense variant E1009D is not reported in ClinVar and is absent from gnomAD. 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 reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.728858 | Disordered | 0.914552 | Binding | 0.325 | 0.885 | 0.500 | -2.958 | Likely Benign | 0.104 | Likely Benign | Likely Benign | 0.054 | Likely Benign | 0.2077 | 0.4817 | -0.37 | Neutral | 0.011 | Benign | 0.017 | Benign | 2.50 | Benign | 0.30 | Tolerated | 3.77 | 5 | 2 | 3 | 0.0 | -14.03 | |||||||||||||||||||||||||||||||||
| c.304T>A | L102M 2D AIThe SynGAP1 missense variant L102M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | -5.033 | Likely Benign | 0.085 | Likely Benign | Likely Benign | 0.129 | Likely Benign | 0.1091 | 0.4176 | 0.12 | Neutral | 0.984 | Probably Damaging | 0.969 | Probably Damaging | 4.14 | Benign | 0.00 | Affected | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||
| c.304T>G | L102V 2D AIThe SynGAP1 missense variant L102V is listed in ClinVar (ID 1925749.0) with an “Uncertain” status and is present in gnomAD (6‑33432169‑T‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This consensus does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | Uncertain | 1 | 6-33432169-T-G | 1 | 6.20e-7 | -4.316 | Likely Benign | 0.068 | Likely Benign | Likely Benign | 0.102 | Likely Benign | 0.1683 | 0.3671 | 0.32 | Neutral | 0.880 | Possibly Damaging | 0.899 | Possibly Damaging | 4.21 | Benign | 0.00 | Affected | 4.32 | 1 | 2 | 1 | 0.4 | -14.03 | ||||||||||||||||||||||||||||
| c.305T>C | L102S 2D AIThe SynGAP1 missense variant L102S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise 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 impact for the L102S 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 | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | -3.260 | Likely Benign | 0.105 | Likely Benign | Likely Benign | 0.174 | Likely Benign | 0.2785 | 0.1752 | 0.54 | Neutral | 0.984 | Probably Damaging | 0.969 | Probably Damaging | 4.18 | Benign | 0.00 | Affected | -3 | -2 | -4.6 | -26.08 | |||||||||||||||||||||||||||||||||||
| c.305T>G | L102W 2D AIThe SynGAP1 missense variant L102W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for L102W, 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 | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | -5.833 | Likely Benign | 0.202 | Likely Benign | Likely Benign | 0.125 | Likely Benign | 0.0821 | 0.3078 | -1.42 | Neutral | 0.996 | Probably Damaging | 0.984 | Probably Damaging | 4.09 | Benign | 0.00 | Affected | -2 | -2 | -4.7 | 73.05 | |||||||||||||||||||||||||||||||||||
| c.306G>C | L102F 2D AIThe SynGAP1 missense variant L102F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | -4.712 | Likely Benign | 0.094 | Likely Benign | Likely Benign | 0.144 | Likely Benign | 0.0863 | 0.3205 | -0.80 | Neutral | 0.984 | Probably Damaging | 0.969 | Probably Damaging | 4.13 | Benign | 0.00 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||
| c.306G>T | L102F 2D AIThe SynGAP1 missense variant L102F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.696014 | Binding | 0.357 | 0.885 | 0.625 | -4.712 | Likely Benign | 0.094 | Likely Benign | Likely Benign | 0.153 | Likely Benign | 0.0863 | 0.3205 | -0.80 | Neutral | 0.984 | Probably Damaging | 0.969 | Probably Damaging | 4.13 | Benign | 0.00 | Affected | 2 | 0 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1343 | 0.5848 | -2.97 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.75 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.3084 | 0.4463 | -2.98 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.78 | Benign | 0.00 | Affected | 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 | 0.3067 | 0.4894 | -3.04 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.78 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.1285 | 0.4784 | -2.92 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.77 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.1319 | 0.3551 | -3.42 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.86 | Benign | 0.00 | Affected | 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 | 0.2055 | 0.6326 | -3.57 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.73 | Benign | 0.00 | Affected | -3 | -3 | 5.4 | 16.04 | ||||||||||||||||||||||||||||||||||||
| c.3400A>C | T1134P 2D AIThe SynGAP1 missense variant T1134P is not reported in ClinVar and is absent from 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 all return benign scores. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are 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 | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -2.993 | Likely Benign | 0.098 | Likely Benign | Likely Benign | 0.164 | Likely Benign | 0.2001 | 0.5165 | -0.57 | Neutral | 0.013 | Benign | 0.022 | Benign | 5.41 | Benign | 0.07 | Tolerated | 0 | -1 | -0.9 | -3.99 | |||||||||||||||||||||||||||||||||||
| c.3400A>G | T1134A 2D AIThe SynGAP1 missense variant T1134A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -3.912 | Likely Benign | 0.090 | Likely Benign | Likely Benign | 0.172 | Likely Benign | 0.3756 | 0.4424 | -0.71 | Neutral | 0.036 | Benign | 0.026 | Benign | 5.70 | Benign | 0.31 | Tolerated | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.3400A>T | T1134S 2D AIThe SynGAP1 missense variant T1134S 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 predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this 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 | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -3.015 | Likely Benign | 0.089 | Likely Benign | Likely Benign | 0.220 | Likely Benign | 0.3189 | 0.4666 | -0.42 | Neutral | 0.007 | Benign | 0.009 | Benign | 5.47 | Benign | 0.09 | Tolerated | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.3401C>A | T1134N 2D AIThe SynGAP1 missense variant T1134N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that T1134N 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 | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -4.368 | Likely Benign | 0.176 | Likely Benign | Likely Benign | 0.193 | Likely Benign | 0.1386 | 0.4870 | -0.34 | Neutral | 0.001 | Benign | 0.001 | Benign | 5.42 | Benign | 0.04 | Affected | 0 | 0 | -2.8 | 13.00 | |||||||||||||||||||||||||||||||||||
| c.3401C>G | T1134S 2D AIThe SynGAP1 missense variant T1134S 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 predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this 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 | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -3.015 | Likely Benign | 0.089 | Likely Benign | Likely Benign | 0.228 | Likely Benign | 0.3189 | 0.4666 | -0.42 | Neutral | 0.007 | Benign | 0.009 | Benign | 5.47 | Benign | 0.09 | Tolerated | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.3401C>T | T1134I 2D AIThe SynGAP1 missense variant T1134I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.885302 | Disordered | 0.813034 | Binding | 0.335 | 0.885 | 0.875 | -4.072 | Likely Benign | 0.416 | Ambiguous | Likely Benign | 0.242 | Likely Benign | 0.1071 | 0.5447 | -1.93 | Neutral | 0.453 | Possibly Damaging | 0.162 | Benign | 5.52 | Benign | 0.44 | Tolerated | 0 | -1 | 5.2 | 12.05 | |||||||||||||||||||||||||||||||||||
| c.388C>A | Q130K 2D AIThe SynGAP1 missense variant Q130K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around benign: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. 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 predictors—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign classification, whereas the pathogenic predictions come from polyPhen‑2 alone. Based on the preponderance of 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 | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -4.656 | Likely Benign | 0.540 | Ambiguous | Likely Benign | 0.058 | Likely Benign | 0.2017 | 0.4473 | -0.41 | Neutral | 0.924 | Possibly Damaging | 0.857 | Possibly Damaging | 4.20 | Benign | 0.07 | Tolerated | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.388C>G | Q130E 2D AIThe SynGAP1 missense variant Q130E is reported in gnomAD (ID 6‑33432685‑C‑G) but has no ClinVar entry. 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, 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 (majority of the same four tools) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms indicates 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 | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | 6-33432685-C-G | 2 | 1.24e-6 | -4.283 | Likely Benign | 0.251 | Likely Benign | Likely Benign | 0.060 | Likely Benign | 0.1620 | 0.2587 | -0.72 | Neutral | 0.924 | Possibly Damaging | 0.857 | Possibly Damaging | 4.19 | Benign | 0.08 | Tolerated | 4.32 | 2 | 2 | 2 | 0.0 | 0.98 | ||||||||||||||||||||||||||||||
| c.389A>C | Q130P 2D AIThe SynGAP1 missense variant Q130P 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 further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available 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 | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -0.659 | Likely Benign | 0.068 | Likely Benign | Likely Benign | 0.213 | Likely Benign | 0.2414 | 0.4466 | -0.10 | Neutral | 0.990 | Probably Damaging | 0.954 | Probably Damaging | 4.15 | Benign | 0.03 | Affected | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.389A>G | Q130R 2D AIThe SynGAP1 missense variant Q130R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus also 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 preponderance of evidence from both general and high‑accuracy predictors points to a benign impact. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -4.043 | Likely Benign | 0.478 | Ambiguous | Likely Benign | 0.166 | Likely Benign | 0.1697 | 0.2343 | -0.32 | Neutral | 0.967 | Probably Damaging | 0.901 | Possibly Damaging | 4.21 | Benign | 0.05 | Affected | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.389A>T | Q130L 2D AIThe SynGAP1 missense variant Q130L is not reported 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 Q130L, 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 | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -3.643 | Likely Benign | 0.278 | Likely Benign | Likely Benign | 0.167 | Likely Benign | 0.0975 | 0.5286 | -1.63 | Neutral | 0.967 | Probably Damaging | 0.901 | Possibly Damaging | 4.11 | Benign | 0.02 | Affected | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.390A>C | Q130H 2D AIThe SynGAP1 missense variant Q130H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective 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 | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -3.828 | Likely Benign | 0.387 | Ambiguous | Likely Benign | 0.074 | Likely Benign | 0.1727 | 0.3970 | -1.09 | Neutral | 0.990 | Probably Damaging | 0.969 | Probably Damaging | 4.10 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.390A>T | Q130H 2D AIThe SynGAP1 missense variant Q130H is not reported in ClinVar and has no entry in gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight benign predictions: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the balance of evidence points to a benign effect for the variant, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.718853 | Binding | 0.306 | 0.885 | 0.375 | -3.828 | Likely Benign | 0.387 | Ambiguous | Likely Benign | 0.074 | Likely Benign | 0.1727 | 0.3970 | -1.09 | Neutral | 0.990 | Probably Damaging | 0.969 | Probably Damaging | 4.10 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1535 | 0.6636 | -1.87 | Neutral | 0.939 | Possibly Damaging | 0.496 | Possibly Damaging | 3.95 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.2095 | 0.3745 | -2.80 | Deleterious | 0.225 | Benign | 0.084 | Benign | 3.96 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.0671 | 0.5365 | -2.48 | Neutral | 0.939 | Possibly Damaging | 0.396 | Benign | 3.90 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.1450 | 0.6621 | -3.18 | Deleterious | 0.127 | Benign | 0.045 | Benign | 3.96 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.3937 | 0.6307 | -2.69 | Deleterious | 0.004 | Benign | 0.003 | Benign | 4.03 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.0719 | 0.5354 | -2.86 | Deleterious | 0.009 | Benign | 0.004 | Benign | 3.91 | Benign | 0.00 | Affected | -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 | 0.2065 | 0.5500 | -3.27 | Deleterious | 0.414 | Benign | 0.063 | Benign | 4.00 | Benign | 0.00 | Affected | 3.77 | 5 | 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 | 0.2065 | 0.5500 | -3.27 | Deleterious | 0.414 | Benign | 0.063 | Benign | 4.00 | Benign | 0.00 | Affected | 3.77 | 5 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||
| c.2473T>A | S825T 2D AIThe SynGAP1 missense variant S825T is not 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 high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two benign, two pathogenic). AlphaMissense‑Optimized, a high‑accuracy model, 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 standard tools (5 pathogenic vs. 4 benign) suggest a pathogenic impact, while the single high‑accuracy model indicates 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 the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.675549 | Disordered | 0.618614 | Binding | 0.384 | 0.886 | 0.750 | -4.659 | Likely Benign | 0.615 | Likely Pathogenic | Likely Benign | 0.155 | Likely Benign | 0.1432 | 0.6658 | -2.26 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.07 | Pathogenic | 0.05 | Affected | 1 | 1 | 0.1 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2473T>C | S825P 2D AIThe SynGAP1 missense variant S825P is not 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 S825P 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 | 0.675549 | Disordered | 0.618614 | Binding | 0.384 | 0.886 | 0.750 | -3.227 | Likely Benign | 0.959 | Likely Pathogenic | Likely Pathogenic | 0.285 | Likely Benign | 0.2060 | 0.5998 | -3.12 | Deleterious | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 1.94 | Pathogenic | 0.02 | Affected | 1 | -1 | -0.8 | 10.04 | |||||||||||||||||||||||||||||||||||
| c.2473T>G | S825A 2D AIThe SynGAP1 missense variant S825A is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on pathogenic are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, while the high‑accuracy AlphaMissense‑Optimized suggests benign and the consensus is neutral. Given the preponderance of pathogenic predictions and the lack of conflicting evidence from ClinVar or population databases, 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. | 0.675549 | Disordered | 0.618614 | Binding | 0.384 | 0.886 | 0.750 | -4.878 | Likely Benign | 0.569 | Likely Pathogenic | Likely Benign | 0.135 | Likely Benign | 0.4794 | 0.5749 | -2.30 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 2.04 | Pathogenic | 0.05 | Affected | 1 | 1 | 2.6 | -16.00 | ||||||||||||||||||||||||||||||||||||
| c.2474C>G | S825W 2D AIThe SynGAP1 missense variant S825W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy methods further support a pathogenic interpretation: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, indicates that S825W 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 | 0.675549 | Disordered | 0.618614 | Binding | 0.384 | 0.886 | 0.750 | -8.396 | Likely Pathogenic | 0.981 | Likely Pathogenic | Likely Pathogenic | 0.316 | Likely Benign | 0.0818 | 0.6083 | -5.25 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 1.91 | Pathogenic | 0.00 | Affected | -2 | -3 | -0.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.2474C>T | S825L 2D AIThe SynGAP1 missense variant S825L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443026‑C‑T). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.675549 | Disordered | 0.618614 | Binding | 0.384 | 0.886 | 0.750 | Uncertain | 1 | 6-33443026-C-T | 1 | 6.20e-7 | -4.987 | Likely Benign | 0.910 | Likely Pathogenic | Ambiguous | 0.249 | Likely Benign | 0.1252 | 0.5747 | -4.30 | Deleterious | 0.999 | Probably Damaging | 0.994 | Probably Damaging | 1.94 | Pathogenic | 0.01 | Affected | 3.77 | 5 | -2 | -3 | 4.6 | 26.08 | ||||||||||||||||||||||||||||
| c.2476G>A | D826N 2D AIThe SynGAP1 missense variant D826N has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on benign effects include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Given the balance of evidence, the majority of high‑confidence predictions and the SGM consensus favor a benign outcome. Therefore, 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 | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -3.663 | Likely Benign | 0.907 | Likely Pathogenic | Ambiguous | 0.154 | Likely Benign | 0.1520 | 0.8248 | -2.24 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.54 | Benign | 0.01 | Affected | 2 | 1 | 0.0 | -0.98 | |||||||||||||||||||||||||||||||||||
| c.2476G>C | D826H 2D AIThe SynGAP1 missense variant D826H is not 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 D826H 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 | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -6.437 | Likely Benign | 0.991 | Likely Pathogenic | Likely Pathogenic | 0.345 | Likely Benign | 0.1757 | 0.8651 | -3.00 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.49 | Pathogenic | 0.00 | Affected | 1 | -1 | 0.3 | 22.05 | |||||||||||||||||||||||||||||||||||
| c.2476G>T | D826Y 2D AIThe SynGAP1 missense variant D826Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect for D826Y. Thus, the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -8.029 | Likely Pathogenic | 0.988 | Likely Pathogenic | Likely Pathogenic | 0.336 | Likely Benign | 0.0683 | 0.7410 | -4.25 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.47 | Pathogenic | 0.00 | Affected | -4 | -3 | 2.2 | 48.09 | |||||||||||||||||||||||||||||||||||
| c.2477A>C | D826A 2D AIThe SynGAP1 D826A missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (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 (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -5.590 | Likely Benign | 0.984 | Likely Pathogenic | Likely Pathogenic | 0.307 | Likely Benign | 0.4463 | 0.7867 | -3.77 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 2.53 | Benign | 0.02 | Affected | 0 | -2 | 5.3 | -44.01 | ||||||||||||||||||||||||||||||||||||
| c.2477A>G | D826G 2D AIThe SynGAP1 D826G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -6.310 | Likely Benign | 0.983 | Likely Pathogenic | Likely Pathogenic | 0.323 | Likely Benign | 0.4251 | 0.7480 | -2.94 | Deleterious | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.51 | Benign | 0.01 | Affected | 1 | -1 | 3.1 | -58.04 | ||||||||||||||||||||||||||||||||||||
| c.2477A>T | D826V 2D AIThe SynGAP1 missense variant D826V 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D826V, and 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 | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -6.918 | Likely Benign | 0.991 | Likely Pathogenic | Likely Pathogenic | 0.428 | Likely Benign | 0.1017 | 0.8023 | -4.64 | Deleterious | 1.000 | Probably Damaging | 0.999 | Probably Damaging | 2.48 | Pathogenic | 0.00 | Affected | -2 | -3 | 7.7 | -15.96 | |||||||||||||||||||||||||||||||||||
| c.2478C>A | D826E 2D AIThe SynGAP1 missense variant D826E is not reported 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 | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -4.172 | Likely Benign | 0.859 | Likely Pathogenic | Ambiguous | 0.164 | Likely Benign | 0.1795 | 0.7687 | -0.66 | Neutral | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.92 | Benign | 0.56 | Tolerated | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2478C>G | D826E 2D AIThe SynGAP1 missense variant D826E is not reported 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. 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 | 0.666105 | Disordered | 0.627309 | Binding | 0.327 | 0.886 | 0.625 | -4.172 | Likely Benign | 0.859 | Likely Pathogenic | Ambiguous | 0.164 | Likely Benign | 0.1795 | 0.7687 | -0.66 | Neutral | 0.997 | Probably Damaging | 0.994 | Probably Damaging | 2.92 | Benign | 0.56 | Tolerated | 3 | 2 | 0.0 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2647C>A | L883I 2D AIThe SynGAP1 missense variant L883I 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, 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 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 | 0.716283 | Disordered | 0.641952 | Binding | 0.334 | 0.886 | 0.250 | -5.046 | Likely Benign | 0.102 | Likely Benign | Likely Benign | 0.049 | Likely Benign | 0.0970 | 0.4093 | -0.26 | Neutral | 0.802 | Possibly Damaging | 0.355 | Benign | 2.66 | Benign | 0.35 | Tolerated | 2 | 2 | 0.7 | 0.00 | |||||||||||||||||||||||||||||||||||
| c.2647C>G | L883V 2D AIThe SynGAP1 missense variant L883V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.716283 | Disordered | 0.641952 | Binding | 0.334 | 0.886 | 0.250 | -4.075 | Likely Benign | 0.079 | Likely Benign | Likely Benign | 0.059 | Likely Benign | 0.1611 | 0.3744 | -0.28 | Neutral | 0.451 | Benign | 0.157 | Benign | 2.67 | Benign | 0.28 | Tolerated | 2 | 1 | 0.4 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.2648T>A | L883Q 2D AIThe SynGAP1 missense variant L883Q is reported in gnomAD (6‑33443200‑T‑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, reports a likely benign classification. High‑accuracy assessments reinforce 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. The variant is therefore 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 | 0.716283 | Disordered | 0.641952 | Binding | 0.334 | 0.886 | 0.250 | 6-33443200-T-A | 3 | 1.86e-6 | -3.559 | Likely Benign | 0.123 | Likely Benign | Likely Benign | 0.129 | Likely Benign | 0.1119 | 0.1505 | -0.51 | Neutral | 0.934 | Possibly Damaging | 0.637 | Possibly Damaging | 2.66 | Benign | 0.11 | Tolerated | 4.32 | 4 | -2 | -2 | -7.3 | 14.97 | ||||||||||||||||||||||||||||||
| c.2648T>C | L883P 2D AIThe SynGAP1 missense variant L883P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.716283 | Disordered | 0.641952 | Binding | 0.334 | 0.886 | 0.250 | -2.572 | Likely Benign | 0.105 | Likely Benign | Likely Benign | 0.074 | Likely Benign | 0.3462 | 0.1658 | -0.58 | Neutral | 0.934 | Possibly Damaging | 0.516 | Possibly Damaging | 2.62 | Benign | 0.21 | Tolerated | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||||||
| c.2648T>G | L883R 2D AIThe SynGAP1 missense variant L883R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for the L883R variant, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.716283 | Disordered | 0.641952 | Binding | 0.334 | 0.886 | 0.250 | -3.026 | Likely Benign | 0.286 | Likely Benign | Likely Benign | 0.110 | Likely Benign | 0.1237 | 0.1147 | -0.83 | Neutral | 0.934 | Possibly Damaging | 0.435 | Benign | 2.73 | Benign | 0.11 | Tolerated | -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 | 0.1957 | 0.3216 | -0.61 | Neutral | 0.174 | Benign | 0.045 | Benign | 4.18 | Benign | 0.24 | Tolerated | 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 | 0.2402 | 0.2643 | -1.08 | Neutral | 0.001 | Benign | 0.002 | Benign | 4.20 | Benign | 0.20 | Tolerated | 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 | 0.1741 | 0.4411 | -1.27 | Neutral | 0.878 | Possibly Damaging | 0.232 | Benign | 4.12 | Benign | 0.03 | Affected | 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 | 0.2011 | 0.4352 | -0.94 | Neutral | 0.748 | Possibly Damaging | 0.170 | Benign | 4.16 | Benign | 0.07 | Tolerated | 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 | 0.2276 | 0.3337 | -1.04 | Neutral | 0.325 | Benign | 0.129 | Benign | 4.18 | Benign | 0.07 | Tolerated | 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 | 0.1738 | 0.5487 | -1.49 | Neutral | 0.494 | Possibly Damaging | 0.170 | Benign | 4.15 | Benign | 0.03 | Affected | -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 | 0.1943 | 0.3844 | -1.04 | Neutral | 0.325 | Benign | 0.045 | Benign | 4.19 | Benign | 0.06 | Tolerated | 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 | 0.1943 | 0.3844 | -1.04 | Neutral | 0.325 | Benign | 0.045 | Benign | 4.19 | Benign | 0.06 | Tolerated | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| 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 | 0.2094 | 0.3596 | -0.21 | Neutral | 0.369 | Benign | 0.120 | Benign | 4.18 | Benign | 0.16 | Tolerated | 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 | 0.2482 | 0.3023 | -0.81 | Neutral | 0.369 | Benign | 0.159 | Benign | 4.16 | Benign | 0.46 | Tolerated | 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 | 0.1627 | 0.4464 | -1.13 | Neutral | 0.812 | Possibly Damaging | 0.298 | Benign | 4.09 | Benign | 0.10 | Tolerated | 3.77 | 5 | 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 | 0.2101 | 0.4487 | -1.10 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.10 | Benign | 0.14 | Tolerated | 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 | 0.2330 | 0.3380 | -1.28 | Neutral | 0.001 | Benign | 0.003 | Benign | 4.15 | Benign | 0.24 | Tolerated | 3.77 | 5 | 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 | 0.1626 | 0.5680 | -1.58 | Neutral | 0.224 | Benign | 0.091 | Benign | 4.13 | Benign | 0.43 | Tolerated | -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 | 0.2112 | 0.3979 | -0.75 | Neutral | 0.411 | Benign | 0.132 | Benign | 4.17 | Benign | 0.29 | Tolerated | 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 | 0.2112 | 0.3979 | -0.75 | Neutral | 0.411 | Benign | 0.132 | Benign | 4.17 | Benign | 0.29 | Tolerated | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1988 | 0.3495 | -0.30 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.64 | Tolerated | 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 | 0.2313 | 0.2923 | -0.45 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.24 | Tolerated | 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 | 0.1422 | 0.4363 | -1.13 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.11 | Benign | 0.02 | Affected | 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 | 0.1978 | 0.4301 | -0.34 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.12 | Benign | 0.04 | Affected | 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 | 0.2237 | 0.3467 | -0.68 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.19 | Benign | 0.05 | Affected | 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 | 0.1409 | 0.5195 | -1.20 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.15 | Benign | 0.02 | Affected | -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 | 0.1969 | 0.3593 | -0.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.07 | Tolerated | 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 | 0.1969 | 0.3593 | -0.38 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.18 | Benign | 0.07 | Tolerated | 3 | 0 | -0.3 | -9.01 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1926 | 0.5861 | -0.92 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.78 | Benign | 0.06 | Tolerated | 3.77 | 5 | 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 | 0.1514 | 0.3717 | -0.59 | Neutral | 0.112 | Benign | 0.041 | Benign | 2.78 | Benign | 0.07 | Tolerated | 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 | 0.2059 | 0.5956 | -0.96 | Neutral | 0.001 | Benign | 0.001 | Benign | 2.69 | Benign | 0.05 | Affected | 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 | 0.1537 | 0.3904 | -1.06 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.73 | Benign | 0.04 | Affected | 3.77 | 5 | 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 | 0.0899 | 0.6837 | -1.10 | Neutral | 0.224 | Benign | 0.091 | Benign | 2.72 | Benign | 0.03 | Affected | -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 | 0.1600 | 0.5269 | -1.14 | Neutral | 0.002 | Benign | 0.003 | Benign | 2.69 | Benign | 0.02 | Affected | 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 | 0.1600 | 0.5269 | -1.14 | Neutral | 0.002 | Benign | 0.003 | Benign | 2.69 | Benign | 0.02 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.3322A>C | S1108R 2D AISynGAP1 missense variant S1108R is not reported in ClinVar (status: None) and is absent from gnomAD (no entry). Prediction tools that classify the variant as benign include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive, as it yields a 2‑vs‑2 split. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available result for this variant. Overall, the computational evidence is mixed, with an equal number of benign and pathogenic calls and no high‑confidence consensus. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict the ClinVar status, which is unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -5.878 | Likely Benign | 0.912 | Likely Pathogenic | Ambiguous | 0.130 | Likely Benign | 0.0864 | 0.3492 | -2.75 | Deleterious | 0.611 | Possibly Damaging | 0.329 | Benign | 2.54 | Benign | 0.04 | Affected | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.3322A>G | S1108G 2D AIThe SynGAP1 missense variant S1108G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (six benign vs three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. 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. | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -6.496 | Likely Benign | 0.126 | Likely Benign | Likely Benign | 0.084 | Likely Benign | 0.2268 | 0.3975 | -2.59 | Deleterious | 0.568 | Possibly Damaging | 0.239 | Benign | 2.46 | Pathogenic | 0.16 | Tolerated | 1 | 0 | 0.4 | -30.03 | ||||||||||||||||||||||||||||||||||||
| c.3322A>T | S1108C 2D AIThe SynGAP1 missense variant S1108C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification, and this conclusion does not contradict any ClinVar status because 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 | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -9.189 | Likely Pathogenic | 0.183 | Likely Benign | Likely Benign | 0.118 | Likely Benign | 0.0992 | 0.5299 | -3.30 | Deleterious | 0.992 | Probably Damaging | 0.820 | Possibly Damaging | 2.42 | Pathogenic | 0.04 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.3323G>A | S1108N 2D AIThe SynGAP1 missense variant S1108N is not reported 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 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 S1108N, 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 | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -6.488 | Likely Benign | 0.250 | Likely Benign | Likely Benign | 0.070 | Likely Benign | 0.1283 | 0.3952 | -2.02 | Neutral | 0.611 | Possibly Damaging | 0.239 | Benign | 2.47 | Pathogenic | 0.06 | Tolerated | 1 | 1 | -2.7 | 27.03 | |||||||||||||||||||||||||||||||||||
| c.3323G>C | S1108T 2D AIThe SynGAP1 missense variant S1108T 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 because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -5.710 | Likely Benign | 0.105 | Likely Benign | Likely Benign | 0.078 | Likely Benign | 0.1304 | 0.5365 | -1.49 | Neutral | 0.393 | Benign | 0.239 | Benign | 2.56 | Benign | 0.25 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.3323G>T | S1108I 2D AIThe SynGAP1 missense variant S1108I is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33443875‑G‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no reported result for this variant. Overall, the balance of evidence (five benign versus four pathogenic predictions) suggests 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. | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | Uncertain | 1 | 6-33443875-G-T | -3.666 | Likely Benign | 0.292 | Likely Benign | Likely Benign | 0.145 | Likely Benign | 0.0949 | 0.4602 | -3.73 | Deleterious | 0.971 | Probably Damaging | 0.604 | Possibly Damaging | 2.44 | Pathogenic | 0.10 | Tolerated | 3.77 | 5 | -2 | -1 | 5.3 | 26.08 | |||||||||||||||||||||||||||||||
| c.3324C>A | S1108R 2D AISynGAP1 missense variant S1108R has no ClinVar record and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 split and therefore unavailable; Foldetta, which would combine FoldX‑MD and Rosetta outputs, has no reported result. Consequently, the evidence is evenly divided, leaving the variant’s functional impact uncertain. The predictions do not contradict any ClinVar status, as none is available. Overall, the variant is most likely of uncertain significance rather than definitively benign or pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -5.878 | Likely Benign | 0.912 | Likely Pathogenic | Ambiguous | 0.109 | Likely Benign | 0.0864 | 0.3492 | -2.75 | Deleterious | 0.611 | Possibly Damaging | 0.329 | Benign | 2.54 | Benign | 0.04 | Affected | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.3324C>G | S1108R 2D AIThe SynGAP1 missense variant S1108R 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 pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, which would assess protein‑folding stability, has no available result for this variant. Overall, the computational evidence is balanced, providing no clear bias toward benign or pathogenic. Thus, the variant’s likely impact remains uncertain, and there is no contradiction with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.852992 | Disordered | 0.949221 | Binding | 0.324 | 0.886 | 0.875 | -5.878 | Likely Benign | 0.912 | Likely Pathogenic | Ambiguous | 0.108 | Likely Benign | 0.0864 | 0.3492 | -2.75 | Deleterious | 0.611 | Possibly Damaging | 0.329 | Benign | 2.54 | Benign | 0.04 | Affected | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.367G>A | A123T 2D AIThe SynGAP1 missense variant A123T is reported as “Likely Benign” in ClinVar and is not present in gnomAD. Prediction tools that assess functional impact all converge on a benign outcome: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. Foldetta results are unavailable. Overall, 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 | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -3.999 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.117 | Likely Benign | 0.1912 | 0.7109 | 0.59 | Neutral | 0.004 | Benign | 0.001 | Benign | 4.29 | Benign | 0.52 | Tolerated | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.367G>C | A123P 2D AIThe SynGAP1 missense variant A123P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -2.930 | Likely Benign | 0.112 | Likely Benign | Likely Benign | 0.166 | Likely Benign | 0.2301 | 0.5999 | -1.14 | Neutral | 0.838 | Possibly Damaging | 0.278 | Benign | 4.14 | Benign | 0.02 | Affected | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.367G>T | A123S 2D AIThe SynGAP1 missense variant A123S 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 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 | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -3.309 | Likely Benign | 0.088 | Likely Benign | Likely Benign | 0.081 | Likely Benign | 0.2979 | 0.6011 | -0.03 | Neutral | 0.131 | Benign | 0.039 | Benign | 4.21 | Benign | 0.28 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.368C>A | A123D 2D AIThe SynGAP1 missense variant A123D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -3.515 | Likely Benign | 0.692 | Likely Pathogenic | Likely Benign | 0.168 | Likely Benign | 0.2325 | 0.2893 | -1.17 | Neutral | 0.718 | Possibly Damaging | 0.218 | Benign | 4.15 | Benign | 0.01 | Affected | 0 | -2 | -5.3 | 44.01 | |||||||||||||||||||||||||||||||||||
| c.368C>G | A123G 2D AIThe SynGAP1 missense variant A123G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -2.799 | Likely Benign | 0.121 | Likely Benign | Likely Benign | 0.065 | Likely Benign | 0.2070 | 0.5039 | -1.34 | Neutral | 0.421 | Benign | 0.074 | Benign | 4.13 | Benign | 0.03 | Affected | 1 | 0 | -2.2 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.368C>T | A123V 2D AIThe SynGAP1 missense variant A123V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.521092 | Disordered | 0.689505 | Binding | 0.324 | 0.886 | 0.750 | -4.119 | Likely Benign | 0.108 | Likely Benign | Likely Benign | 0.040 | Likely Benign | 0.1549 | 0.6874 | -0.77 | Neutral | 0.010 | Benign | 0.003 | Benign | 4.15 | Benign | 0.02 | Affected | 0 | 0 | 2.4 | 28.05 | |||||||||||||||||||||||||||||||||||
| c.2308C>A | Q770K 2D AIThe SynGAP1 missense variant Q770K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -4.768 | Likely Benign | 0.367 | Ambiguous | Likely Benign | 0.106 | Likely Benign | 0.1984 | 0.4737 | -0.72 | Neutral | 0.002 | Benign | 0.003 | Benign | 4.20 | Benign | 0.14 | Tolerated | 1 | 1 | -0.4 | 0.04 | |||||||||||||||||||||||||||||||||||
| c.2308C>G | Q770E 2D AIThe SynGAP1 missense variant Q770E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -4.782 | Likely Benign | 0.201 | Likely Benign | Likely Benign | 0.109 | Likely Benign | 0.1465 | 0.2833 | -0.82 | Neutral | 0.002 | Benign | 0.003 | Benign | 4.19 | Benign | 0.04 | Affected | 2 | 2 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.2309A>C | Q770P 2D AIThe SynGAP1 missense variant Q770P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q770P, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -3.948 | Likely Benign | 0.087 | Likely Benign | Likely Benign | 0.178 | Likely Benign | 0.2435 | 0.5717 | -1.00 | Neutral | 0.748 | Possibly Damaging | 0.170 | Benign | 4.10 | Benign | 0.02 | Affected | 0 | -1 | 1.9 | -31.01 | |||||||||||||||||||||||||||||||||||
| c.2309A>G | Q770R 2D AIThe SynGAP1 missense variant Q770R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the collective evidence strongly suggests that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -3.873 | Likely Benign | 0.344 | Ambiguous | Likely Benign | 0.175 | Likely Benign | 0.1610 | 0.2580 | -1.38 | Neutral | 0.194 | Benign | 0.071 | Benign | 4.14 | Benign | 0.07 | Tolerated | 1 | 1 | -1.0 | 28.06 | |||||||||||||||||||||||||||||||||||
| c.2309A>T | Q770L 2D AIThe SynGAP1 missense variant Q770L is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q770L, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -5.524 | Likely Benign | 0.521 | Ambiguous | Likely Benign | 0.197 | Likely Benign | 0.0776 | 0.6230 | -2.17 | Neutral | 0.095 | Benign | 0.030 | Benign | 4.14 | Benign | 0.01 | Affected | -2 | -2 | 7.3 | -14.97 | |||||||||||||||||||||||||||||||||||
| c.2310G>C | Q770H 2D AIThe SynGAP1 missense variant Q770H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for Q770H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -4.241 | Likely Benign | 0.270 | Likely Benign | Likely Benign | 0.093 | Likely Benign | 0.1579 | 0.4344 | -1.27 | Neutral | 0.962 | Probably Damaging | 0.515 | Possibly Damaging | 4.11 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.2310G>T | Q770H 2D AIThe SynGAP1 missense variant Q770H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.436924 | Structured | 0.923732 | Binding | 0.328 | 0.887 | 0.250 | -4.241 | Likely Benign | 0.270 | Likely Benign | Likely Benign | 0.093 | Likely Benign | 0.1579 | 0.4344 | -1.27 | Neutral | 0.962 | Probably Damaging | 0.515 | Possibly Damaging | 4.11 | Benign | 0.01 | Affected | 3 | 0 | 0.3 | 9.01 | |||||||||||||||||||||||||||||||||||
| c.2332A>C | N778H 2D AIThe SynGAP1 missense variant N778H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | -4.761 | Likely Benign | 0.172 | Likely Benign | Likely Benign | 0.100 | Likely Benign | 0.1400 | 0.7220 | -1.62 | Neutral | 0.991 | Probably Damaging | 0.980 | Probably Damaging | 4.17 | Benign | 0.04 | Affected | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||
| c.2332A>G | N778D 2D AIThe SynGAP1 missense variant N778D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | -4.838 | Likely Benign | 0.446 | Ambiguous | Likely Benign | 0.093 | Likely Benign | 0.1896 | 0.4528 | -0.86 | Neutral | 0.843 | Possibly Damaging | 0.893 | Possibly Damaging | 4.21 | Benign | 0.15 | Tolerated | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.2332A>T | N778Y 2D AIThe SynGAP1 missense variant N778Y is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). AlphaMissense‑Default is uncertain, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | -5.723 | Likely Benign | 0.421 | Ambiguous | Likely Benign | 0.175 | Likely Benign | 0.0589 | 0.6139 | -2.48 | Neutral | 0.991 | Probably Damaging | 0.980 | Probably Damaging | 4.16 | Benign | 0.02 | Affected | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||
| c.2333A>C | N778T 2D AIThe SynGAP1 missense variant N778T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | -3.820 | Likely Benign | 0.222 | Likely Benign | Likely Benign | 0.110 | Likely Benign | 0.1441 | 0.7395 | -1.52 | Neutral | 0.925 | Possibly Damaging | 0.932 | Probably Damaging | 4.23 | Benign | 0.09 | Tolerated | 0 | 0 | 2.8 | -13.00 | |||||||||||||||||||||||||||||||||||
| c.2333A>G | N778S 2D AIThe SynGAP1 missense variant N778S is reported in gnomAD (ID 6‑33442491‑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 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 assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | 6-33442491-A-G | 1 | 1.28e-6 | -2.711 | Likely Benign | 0.097 | Likely Benign | Likely Benign | 0.137 | Likely Benign | 0.4285 | 0.6890 | -0.61 | Neutral | 0.843 | Possibly Damaging | 0.893 | Possibly Damaging | 4.32 | Benign | 0.86 | Tolerated | 3.64 | 6 | 1 | 1 | 2.7 | -27.03 | ||||||||||||||||||||||||||||||
| c.2333A>T | N778I 2D AIThe SynGAP1 missense variant N778I is reported in gnomAD (ID 6‑33442491‑A‑T) but has no ClinVar entry. 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, 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 (majority of the four high‑accuracy predictors) 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, 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 | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | 6-33442491-A-T | -6.659 | Likely Benign | 0.622 | Likely Pathogenic | Likely Benign | 0.150 | Likely Benign | 0.0628 | 0.6128 | -2.48 | Neutral | 0.991 | Probably Damaging | 0.980 | Probably Damaging | 4.17 | Benign | 0.02 | Affected | 3.64 | 6 | -3 | -2 | 8.0 | -0.94 | ||||||||||||||||||||||||||||||||
| c.2334C>A | N778K 2D AIThe SynGAP1 missense variant N778K is catalogued in gnomAD (ID 6‑33442492‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM; pathogenic predictions 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 outcome, reflecting the majority of benign calls. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, and Foldetta data are not available. Overall, the majority of evidence points toward a benign effect, and this is consistent with the lack of a ClinVar pathogenic classification. 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 | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | 6-33442492-C-A | -6.768 | Likely Benign | 0.798 | Likely Pathogenic | Ambiguous | 0.113 | Likely Benign | 0.2037 | 0.5883 | -1.57 | Neutral | 0.925 | Possibly Damaging | 0.932 | Probably Damaging | 4.27 | Benign | 0.18 | Tolerated | 3.64 | 6 | 0 | 1 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||||
| c.2334C>G | N778K 2D AIThe SynGAP1 missense variant N778K has no ClinVar record and is not listed in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the preponderance of evidence points to a benign effect. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.494003 | Structured | 0.853922 | Binding | 0.288 | 0.887 | 0.500 | -6.768 | Likely Benign | 0.798 | Likely Pathogenic | Ambiguous | 0.114 | Likely Benign | 0.2037 | 0.5883 | -1.57 | Neutral | 0.925 | Possibly Damaging | 0.932 | Probably Damaging | 4.27 | Benign | 0.18 | Tolerated | 3.64 | 6 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||
| c.256G>A | V86I 2D AIThe SynGAP1 missense variant V86I is listed in ClinVar (ID 588267.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the variant as benign or likely benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the majority of predictions indicate that V86I is most likely benign, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | Uncertain | 1 | -4.726 | Likely Benign | 0.338 | Likely Benign | Likely Benign | 0.076 | Likely Benign | 0.0887 | 0.4417 | -0.31 | Neutral | 0.267 | Benign | 0.097 | Benign | 3.94 | Benign | 0.00 | Affected | 4.32 | 1 | 4 | 3 | 0.3 | 14.03 | |||||||||||||||||||||||||||||||
| c.256G>C | V86L 2D AIThe SynGAP1 missense variant V86L is reported in ClinVar as “not listed” and is present in the gnomAD database (ID 6‑33425864‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | 6-33425864-G-C | 1 | 6.20e-7 | -3.658 | Likely Benign | 0.965 | Likely Pathogenic | Likely Pathogenic | 0.081 | Likely Benign | 0.1121 | 0.5386 | -0.84 | Neutral | 0.267 | Benign | 0.097 | Benign | 3.85 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | -0.4 | 14.03 | ||||||||||||||||||||||||||||||
| c.256G>T | V86F 2D AIThe SynGAP1 missense variant V86F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | -5.011 | Likely Benign | 0.981 | Likely Pathogenic | Likely Pathogenic | 0.126 | Likely Benign | 0.0755 | 0.4078 | -1.54 | Neutral | 0.824 | Possibly Damaging | 0.403 | Benign | 3.75 | Benign | 0.00 | Affected | -1 | -1 | -1.4 | 48.04 | |||||||||||||||||||||||||||||||||||
| c.257T>A | V86D 2D AIThe SynGAP1 missense variant V86D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on benign impact include REVEL, PROVEAN, and FATHMM, whereas those that agree on pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans benign (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, whereas the high‑accuracy consensus suggests benign. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for V86D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | -7.141 | In-Between | 0.999 | Likely Pathogenic | Likely Pathogenic | 0.147 | Likely Benign | 0.1590 | 0.1047 | -2.38 | Neutral | 0.824 | Possibly Damaging | 0.485 | Possibly Damaging | 3.73 | Benign | 0.00 | Affected | -2 | -3 | -7.7 | 15.96 | ||||||||||||||||||||||||||||||||||||
| c.257T>C | V86A 2D AIThe SynGAP1 missense variant V86A has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Pathogenic predictions arise from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight a split: AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools (six benign vs. three pathogenic) suggest the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | -3.022 | Likely Benign | 0.991 | Likely Pathogenic | Likely Pathogenic | 0.059 | Likely Benign | 0.3205 | 0.2723 | -1.35 | Neutral | 0.267 | Benign | 0.153 | Benign | 3.80 | Benign | 0.00 | Affected | 0 | 0 | -2.4 | -28.05 | |||||||||||||||||||||||||||||||||||
| c.257T>G | V86G 2D AIThe SynGAP1 missense variant V86G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which evaluates protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence (five pathogenic versus four benign predictions) indicates that V86G is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.685117 | Disordered | 0.552911 | Binding | 0.295 | 0.887 | 0.500 | -4.212 | Likely Benign | 0.989 | Likely Pathogenic | Likely Pathogenic | 0.130 | Likely Benign | 0.2321 | 0.2547 | -2.50 | Deleterious | 0.307 | Benign | 0.824 | Possibly Damaging | 3.74 | Benign | 0.00 | Affected | -1 | -3 | -4.6 | -42.08 | ||||||||||||||||||||||||||||||||||||
| 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 | 0.1604 | 0.7550 | -1.42 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.67 | Benign | 0.10 | Tolerated | 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 | 0.1994 | 0.4375 | -1.39 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 2.70 | Benign | 0.47 | Tolerated | 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 | 0.0661 | 0.5998 | -2.26 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 2.66 | Benign | 0.05 | Affected | -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 | 0.1451 | 0.7930 | -0.78 | Neutral | 0.997 | Probably Damaging | 0.989 | Probably Damaging | 2.77 | Benign | 0.58 | Tolerated | 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 | 0.3980 | 0.7620 | -0.49 | Neutral | 0.997 | Probably Damaging | 0.983 | Probably Damaging | 2.97 | Benign | 0.38 | Tolerated | 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 | 0.0781 | 0.6279 | -2.14 | Neutral | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.67 | Benign | 0.02 | Affected | -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 | 0.2147 | 0.6121 | -1.52 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.73 | Benign | 0.18 | Tolerated | 3.77 | 5 | 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 | 0.2147 | 0.6121 | -1.52 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 2.73 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0 | 1 | -0.4 | 14.07 | |||||||||||||||||||||||||||||||||
| c.358G>A | G120S 2D AIThe SynGAP1 missense variant G120S is reported in gnomAD (variant ID 6-33432223‑G‑A) but has no ClinVar entry. Functional prediction tools uniformly classify the change 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. 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, a protein‑folding stability predictor, was not available for this variant. Overall, the evidence strongly supports a benign classification, and there is 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 | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | 6-33432223-G-A | 1 | 6.20e-7 | -3.558 | Likely Benign | 0.082 | Likely Benign | Likely Benign | 0.034 | Likely Benign | 0.2841 | 0.4713 | 0.07 | Neutral | 0.020 | Benign | 0.012 | Benign | 4.29 | Benign | 0.91 | Tolerated | 3.61 | 5 | 0 | 1 | -0.4 | 30.03 | ||||||||||||||||||||||||||||||
| c.358G>C | G120R 2D AIThe SynGAP1 missense variant G120R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only AlphaMissense‑Default predicts a pathogenic outcome. When predictions are grouped, the benign consensus includes eight tools, whereas the pathogenic consensus contains a single tool. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a likely benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that G120R 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 | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | -4.406 | Likely Benign | 0.745 | Likely Pathogenic | Likely Benign | 0.022 | Likely Benign | 0.1050 | 0.4345 | -0.33 | Neutral | 0.089 | Benign | 0.047 | Benign | 4.26 | Benign | 0.14 | Tolerated | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.358G>T | G120C 2D AIThe SynGAP1 missense variant G120C is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | -5.979 | Likely Benign | 0.179 | Likely Benign | Likely Benign | 0.041 | Likely Benign | 0.1376 | 0.4225 | -0.73 | Neutral | 0.410 | Benign | 0.146 | Benign | 4.20 | Benign | 0.10 | Tolerated | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||||
| c.359G>A | G120D 2D AIThe SynGAP1 missense variant G120D is not reported 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 evidence overwhelmingly supports a benign classification, 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 | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | -3.483 | Likely Benign | 0.465 | Ambiguous | Likely Benign | 0.037 | Likely Benign | 0.1847 | 0.2024 | -0.57 | Neutral | 0.165 | Benign | 0.034 | Benign | 4.25 | Benign | 0.21 | Tolerated | 1 | -1 | -3.1 | 58.04 | |||||||||||||||||||||||||||||||||||
| c.359G>C | G120A 2D AIThe SynGAP1 missense variant G120A 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 | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | -3.477 | Likely Benign | 0.062 | Likely Benign | Likely Benign | 0.027 | Likely Benign | 0.4003 | 0.4565 | 0.29 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.37 | Benign | 1.00 | Tolerated | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.359G>T | G120V 2D AIThe SynGAP1 missense variant G120V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.707965 | Disordered | 0.659993 | Binding | 0.359 | 0.887 | 0.750 | -4.571 | Likely Benign | 0.107 | Likely Benign | Likely Benign | 0.036 | Likely Benign | 0.1321 | 0.3883 | -0.68 | Neutral | 0.000 | Benign | 0.000 | Benign | 4.28 | Benign | 0.19 | Tolerated | -1 | -3 | 4.6 | 42.08 | |||||||||||||||||||||||||||||||||||
| c.364C>A | P122T 2D AIThe SynGAP1 missense variant P122T 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 P122T 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 | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | -3.954 | Likely Benign | 0.088 | Likely Benign | Likely Benign | 0.186 | Likely Benign | 0.2068 | 0.5270 | -1.43 | Neutral | 0.580 | Possibly Damaging | 0.185 | Benign | 4.19 | Benign | 0.13 | Tolerated | 0 | -1 | 0.9 | 3.99 | |||||||||||||||||||||||||||||||||||
| c.364C>G | P122A 2D AIThe SynGAP1 missense variant P122A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the substitution 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 | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | -3.105 | Likely Benign | 0.060 | Likely Benign | Likely Benign | 0.086 | Likely Benign | 0.3991 | 0.4286 | -1.66 | Neutral | 0.363 | Benign | 0.096 | Benign | 4.27 | Benign | 1.00 | Tolerated | 1 | -1 | 3.4 | -26.04 | |||||||||||||||||||||||||||||||||||
| c.364C>T | P122S 2D AIThe SynGAP1 missense variant P122S is catalogued in gnomAD (ID 6‑33432229‑C‑T) 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 classification, and this is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | 6-33432229-C-T | 1 | 6.20e-7 | -3.389 | Likely Benign | 0.098 | Likely Benign | Likely Benign | 0.091 | Likely Benign | 0.4009 | 0.4759 | -1.13 | Neutral | 0.036 | Benign | 0.025 | Benign | 4.22 | Benign | 0.31 | Tolerated | 3.61 | 5 | -1 | 1 | 0.8 | -10.04 | ||||||||||||||||||||||||||||||
| c.365C>A | P122H 2D AIThe SynGAP1 missense variant P122H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including the high‑accuracy tools, points to a benign effect for P122H. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | -4.993 | Likely Benign | 0.321 | Likely Benign | Likely Benign | 0.096 | Likely Benign | 0.2306 | 0.4213 | -1.82 | Neutral | 0.996 | Probably Damaging | 0.750 | Possibly Damaging | 4.14 | Benign | 0.03 | Affected | 0 | -2 | -1.6 | 40.02 | |||||||||||||||||||||||||||||||||||
| c.365C>G | P122R 2D AIThe SynGAP1 missense variant P122R has no ClinVar record and is not listed in gnomAD. 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) which reports “Likely Benign.” Pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the balance of evidence favors a benign effect for P122R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | -4.981 | Likely Benign | 0.572 | Likely Pathogenic | Likely Benign | 0.132 | Likely Benign | 0.1796 | 0.2804 | -1.74 | Neutral | 0.952 | Possibly Damaging | 0.521 | Possibly Damaging | 4.18 | Benign | 0.05 | Affected | 0 | -2 | -2.9 | 59.07 | |||||||||||||||||||||||||||||||||||
| c.365C>T | P122L 2D AIThe SynGAP1 missense variant P122L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and 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, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign 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 | 0.618285 | Disordered | 0.672358 | Binding | 0.400 | 0.887 | 0.750 | -3.810 | Likely Benign | 0.181 | Likely Benign | Likely Benign | 0.167 | Likely Benign | 0.2657 | 0.6362 | -2.92 | Deleterious | 0.906 | Possibly Damaging | 0.420 | Benign | 4.16 | Benign | 0.05 | Affected | -3 | -3 | 5.4 | 16.04 | |||||||||||||||||||||||||||||||||||
| c.2326G>A | G776S 2D AIThe SynGAP1 missense variant G776S is reported in ClinVar as “Not submitted” and is present in gnomAD (variant ID 6-33442484-G-A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic 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. No Foldetta stability analysis is available for this variant. Overall, the majority of predictive evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | 6-33442484-G-A | 1 | 1.28e-6 | -3.334 | Likely Benign | 0.147 | Likely Benign | Likely Benign | 0.163 | Likely Benign | 0.2539 | 0.5785 | -1.21 | Neutral | 0.997 | Probably Damaging | 0.992 | Probably Damaging | 4.28 | Benign | 0.13 | Tolerated | 3.64 | 6 | 0 | 1 | -0.4 | 30.03 | ||||||||||||||||||||||||||||||
| c.2326G>C | G776R 2D AIThe SynGAP1 missense variant G776R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the Foldetta protein‑folding stability assessment is unavailable for this variant. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | -6.209 | Likely Benign | 0.886 | Likely Pathogenic | Ambiguous | 0.181 | Likely Benign | 0.0932 | 0.5115 | -2.28 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 4.22 | Benign | 0.01 | Affected | -3 | -2 | -4.1 | 99.14 | |||||||||||||||||||||||||||||||||||
| c.2326G>T | G776C 2D AIThe SynGAP1 missense variant G776C is not reported in ClinVar but is present in gnomAD (ID 6‑33442484‑G‑T). Prediction tools cluster into benign (REVEL, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). Two tools (ESM1b, AlphaMissense‑Default) return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the single high‑accuracy tool suggests benign. Given the preponderance of pathogenic predictions and the absence of a ClinVar entry, the variant is most likely pathogenic and does not contradict any existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | 6-33442484-G-T | -7.974 | In-Between | 0.380 | Ambiguous | Likely Benign | 0.181 | Likely Benign | 0.1235 | 0.4403 | -2.59 | Deleterious | 1.000 | Probably Damaging | 0.998 | Probably Damaging | 4.15 | Benign | 0.01 | Affected | 3.64 | 6 | -3 | -3 | 2.9 | 46.09 | |||||||||||||||||||||||||||||||||
| c.2327G>A | G776D 2D AIThe SynGAP1 missense variant G776D is catalogued in gnomAD (ID 6‑33442485‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates benign. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G776D, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | 6-33442485-G-A | 0.388 | Likely Benign | 0.566 | Likely Pathogenic | Likely Benign | 0.188 | Likely Benign | 0.1835 | 0.2971 | 0.16 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 4.30 | Benign | 0.10 | Tolerated | 3.64 | 6 | -1 | 1 | -3.1 | 58.04 | ||||||||||||||||||||||||||||||||
| c.2327G>C | G776A 2D AIThe SynGAP1 missense variant G776A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G776A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | -5.275 | Likely Benign | 0.296 | Likely Benign | Likely Benign | 0.173 | Likely Benign | 0.3648 | 0.4971 | -1.82 | Neutral | 0.992 | Probably Damaging | 0.987 | Probably Damaging | 4.26 | Benign | 0.03 | Affected | 1 | 0 | 2.2 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2327G>T | G776V 2D AIThe SynGAP1 missense variant G776V is listed in gnomAD (ID 6‑33442485‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no result for this variant. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also indicates a likely benign outcome; Foldetta data are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.377384 | Structured | 0.886983 | Binding | 0.296 | 0.888 | 0.250 | 6-33442485-G-T | -6.541 | Likely Benign | 0.515 | Ambiguous | Likely Benign | 0.180 | Likely Benign | 0.0993 | 0.4223 | -2.25 | Neutral | 0.999 | Probably Damaging | 0.998 | Probably Damaging | 4.19 | Benign | 0.01 | Affected | 3.64 | 6 | -3 | -1 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||
| c.250C>A | R84S 2D  AIThe SynGAP1 missense variant R84S is not reported in ClinVar and has no gnomAD entry. Prediction tools show mixed results: benign predictions come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta stability analysis is unavailable. Overall, the majority of tools lean toward a benign interpretation, but a substantial subset predicts pathogenicity, leaving the variant’s effect uncertain. Based on the current predictions, R84S is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | -6.233 | Likely Benign | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.103 | Likely Benign | 0.2966 | 0.4139 | -2.18 | Neutral | 0.962 | Probably Damaging | 0.726 | Possibly Damaging | 3.71 | Benign | 0.00 | Affected | 0 | -1 | 3.7 | -69.11 | |||||||||||||||||||||||||||||||||||
| c.250C>G | R84G 2D AIThe SynGAP1 missense variant R84G is listed in ClinVar with an “Uncertain” significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the majority of available predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar status of “Uncertain.” Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | Uncertain | 1 | -6.627 | Likely Benign | 0.989 | Likely Pathogenic | Likely Pathogenic | 0.139 | Likely Benign | 0.3387 | 0.3391 | -2.64 | Deleterious | 0.962 | Probably Damaging | 0.726 | Possibly Damaging | 3.68 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | -2 | 4.1 | -99.14 | ||||||||||||||||||||||||||||||||
| c.250C>T | R84C 2D  AIThe SynGAP1 missense variant R84C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R84C is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | -9.044 | Likely Pathogenic | 0.984 | Likely Pathogenic | Likely Pathogenic | 0.243 | Likely Benign | 0.3281 | 0.3657 | -3.25 | Deleterious | 0.999 | Probably Damaging | 0.876 | Possibly Damaging | 3.66 | Benign | 0.00 | Affected | -4 | -3 | 7.0 | -53.05 | |||||||||||||||||||||||||||||||||||
| c.251G>A | R84H 2D  AIThe SynGAP1 missense variant R84H is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Overall, the majority of standard predictors (four pathogenic vs. three benign) lean toward a pathogenic interpretation, and the high‑accuracy consensus does not overturn this trend. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | -7.333 | In-Between | 0.935 | Likely Pathogenic | Ambiguous | 0.147 | Likely Benign | 0.2739 | 0.2426 | -1.77 | Neutral | 0.995 | Probably Damaging | 0.840 | Possibly Damaging | 3.68 | Benign | 0.00 | Affected | 2 | 0 | 1.3 | -19.05 | ||||||||||||||||||||||||||||||||||||
| c.251G>C | R84P 2D AIThe SynGAP1 missense variant R84P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b is uncertain and does not influence the consensus. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R84P is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | -7.959 | In-Between | 0.994 | Likely Pathogenic | Likely Pathogenic | 0.157 | Likely Benign | 0.1978 | 0.4231 | -2.50 | Deleterious | 0.989 | Probably Damaging | 0.859 | Possibly Damaging | 3.67 | Benign | 0.00 | Affected | 0 | -2 | 2.9 | -59.07 | ||||||||||||||||||||||||||||||||||||
| c.251G>T | R84L 2D AIThe SynGAP1 missense variant R84L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R84L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.666105 | Disordered | 0.529205 | Binding | 0.298 | 0.888 | 0.500 | -7.579 | In-Between | 0.987 | Likely Pathogenic | Likely Pathogenic | 0.120 | Likely Benign | 0.1595 | 0.4653 | -2.75 | Deleterious | 0.962 | Probably Damaging | 0.726 | Possibly Damaging | 3.70 | Benign | 0.00 | Affected | -3 | -2 | 8.3 | -43.03 | ||||||||||||||||||||||||||||||||||||
| c.253A>C | T85P 2D AIThe SynGAP1 missense variant T85P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are not provided. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -8.406 | Likely Pathogenic | 0.978 | Likely Pathogenic | Likely Pathogenic | 0.125 | Likely Benign | 0.1499 | 0.4485 | -2.28 | Neutral | 0.813 | Possibly Damaging | 0.053 | Benign | 3.80 | Benign | 0.00 | Affected | 0 | -1 | -0.9 | -3.99 | ||||||||||||||||||||||||||||||||||||
| c.253A>G | T85A 2D AIThe SynGAP1 missense variant T85A is not reported in ClinVar and is absent from gnomAD. Consensus and most in‑silico predictors classify it as benign: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all indicate a benign effect. In contrast, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic impact. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized reports a pathogenic change, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools and the consensus prediction lean toward a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -4.803 | Likely Benign | 0.978 | Likely Pathogenic | Likely Pathogenic | 0.101 | Likely Benign | 0.3155 | 0.3517 | -1.79 | Neutral | 0.060 | Benign | 0.004 | Benign | 3.88 | Benign | 0.00 | Affected | 1 | 0 | 2.5 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.253A>T | T85S 2D AIThe SynGAP1 missense variant T85S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of conventional predictors lean toward a benign impact, but the high‑accuracy AlphaMissense‑Optimized tool suggests pathogenicity, creating a conflict. No ClinVar entry exists, so there is no reported status to contradict. Based on the collective evidence, the variant is most likely benign, though the high‑accuracy prediction indicates uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -4.171 | Likely Benign | 0.973 | Likely Pathogenic | Likely Pathogenic | 0.103 | Likely Benign | 0.2590 | 0.3569 | -1.37 | Neutral | 0.113 | Benign | 0.011 | Benign | 3.87 | Benign | 0.00 | Affected | 1 | 1 | -0.1 | -14.03 | |||||||||||||||||||||||||||||||||||
| c.254C>A | T85K 2D AIThe SynGAP1 missense variant T85K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields an equal split (2 pathogenic, 2 benign) and is therefore considered unavailable; Foldetta results are not provided and are likewise unavailable. Overall, the majority of available predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -9.278 | Likely Pathogenic | 0.992 | Likely Pathogenic | Likely Pathogenic | 0.127 | Likely Benign | 0.0823 | 0.2796 | -2.32 | Neutral | 0.588 | Possibly Damaging | 0.036 | Benign | 3.88 | Benign | 0.00 | Affected | 0 | -1 | -3.2 | 27.07 | ||||||||||||||||||||||||||||||||||||
| c.254C>G | T85R 2D AIThe SynGAP1 missense variant T85R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessment gives AlphaMissense‑Optimized a pathogenic score, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (benign)—leans toward benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the balance of evidence tilts toward a benign interpretation, with no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign, though the presence of pathogenic predictions from several tools indicates that further functional validation would be prudent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -7.936 | In-Between | 0.989 | Likely Pathogenic | Likely Pathogenic | 0.116 | Likely Benign | 0.0754 | 0.2482 | -2.32 | Neutral | 0.813 | Possibly Damaging | 0.072 | Benign | 3.91 | Benign | 0.00 | Affected | -1 | -1 | -3.8 | 55.08 | ||||||||||||||||||||||||||||||||||||
| c.254C>T | T85I 2D AIThe SynGAP1 missense variant T85I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized also predicts pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that T85I is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.680603 | Disordered | 0.542004 | Binding | 0.288 | 0.888 | 0.500 | -9.310 | Likely Pathogenic | 0.998 | Likely Pathogenic | Likely Pathogenic | 0.113 | Likely Benign | 0.0634 | 0.5443 | -2.50 | Deleterious | 0.813 | Possibly Damaging | 0.072 | Benign | 3.82 | Benign | 0.00 | Affected | 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 | 0.3187 | 0.4070 | -0.93 | Neutral | 0.005 | Benign | 0.007 | Benign | 4.17 | Benign | 0.18 | Tolerated | 4.32 | 2 | -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 | 0.3141 | 0.3446 | -0.01 | Neutral | 0.994 | Probably Damaging | 0.626 | Possibly Damaging | 4.21 | Benign | 0.36 | Tolerated | 4.32 | 2 | 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 | 0.2145 | 0.5533 | -0.76 | Neutral | 0.996 | Probably Damaging | 0.828 | Possibly Damaging | 4.14 | Benign | 0.17 | Tolerated | 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 | 0.1964 | 0.5093 | -0.99 | Neutral | 0.959 | Probably Damaging | 0.586 | Possibly Damaging | 4.15 | Benign | 0.75 | Tolerated | 4.32 | 2 | -2 | -3 | 8.3 | -43.03 | ||||||||||||||||||||||||||||
| 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 | 0.3310 | 0.3693 | -2.79 | Deleterious | 0.997 | Probably Damaging | 0.993 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.1238 | 0.3700 | -3.15 | Deleterious | 1.000 | Probably Damaging | 0.996 | Probably Damaging | 2.70 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.2962 | 0.2751 | -1.43 | Neutral | 0.998 | Probably Damaging | 0.988 | Probably Damaging | 2.73 | Benign | 0.02 | Affected | 3.77 | 5 | 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 | 0.1988 | 0.4524 | -2.55 | Deleterious | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.71 | Benign | 0.01 | Affected | 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 | 0.1909 | 0.4568 | -2.38 | Neutral | 0.997 | Probably Damaging | 0.993 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | -3 | -2 | 8.3 | -43.03 | |||||||||||||||||||||||||||||||||||
| c.361G>A | A121T 2D AIThe SynGAP1 missense variant A121T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | -3.955 | Likely Benign | 0.070 | Likely Benign | Likely Benign | 0.059 | Likely Benign | 0.1792 | 0.7305 | -0.25 | Neutral | 0.063 | Benign | 0.026 | Benign | 4.10 | Benign | 0.05 | Affected | 1 | 0 | -2.5 | 30.03 | |||||||||||||||||||||||||||||||||||
| c.361G>C | A121P 2D AIThe SynGAP1 missense variant A121P 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 the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that A121P 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 | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | -3.210 | Likely Benign | 0.077 | Likely Benign | Likely Benign | 0.062 | Likely Benign | 0.2197 | 0.6196 | 0.95 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.18 | Benign | 0.03 | Affected | 1 | -1 | -3.4 | 26.04 | |||||||||||||||||||||||||||||||||||
| c.361G>T | A121S 2D AIThe SynGAP1 missense variant A121S 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 also support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” 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 | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | -3.027 | Likely Benign | 0.078 | Likely Benign | Likely Benign | 0.067 | Likely Benign | 0.2805 | 0.5817 | -0.06 | Neutral | 0.002 | Benign | 0.002 | Benign | 4.18 | Benign | 0.40 | Tolerated | 1 | 1 | -2.6 | 16.00 | |||||||||||||||||||||||||||||||||||
| c.362C>A | A121D 2D AIThe SynGAP1 missense variant A121D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | -3.626 | Likely Benign | 0.595 | Likely Pathogenic | Likely Benign | 0.096 | Likely Benign | 0.1876 | 0.1945 | -0.89 | Neutral | 0.244 | Benign | 0.050 | Benign | 4.06 | Benign | 0.03 | Affected | 0 | -2 | -5.3 | 44.01 | |||||||||||||||||||||||||||||||||||
| c.362C>G | A121G 2D AIThe SynGAP1 missense variant A121G is catalogued in gnomAD (ID 6‑33432227‑C‑G) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool examined—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No 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, did not provide a result for this variant, so its status remains unavailable. Overall, the evidence strongly supports a benign effect for A121G, and this conclusion does not contradict any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | 6-33432227-C-G | 4 | 2.48e-6 | -3.123 | Likely Benign | 0.099 | Likely Benign | Likely Benign | 0.073 | Likely Benign | 0.2407 | 0.5271 | -0.52 | Neutral | 0.118 | Benign | 0.026 | Benign | 4.06 | Benign | 0.07 | Tolerated | 3.61 | 5 | 0 | 1 | -2.2 | -14.03 | ||||||||||||||||||||||||||||||
| c.362C>T | A121V 2D AIThe SynGAP1 missense variant A121V is reported in gnomAD (ID 6‑33432227‑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 variant 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 supports a benign classification for A121V, 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 | 0.779859 | Disordered | 0.661304 | Binding | 0.362 | 0.888 | 0.750 | 6-33432227-C-T | 3 | 1.86e-6 | -3.818 | Likely Benign | 0.086 | Likely Benign | Likely Benign | 0.046 | Likely Benign | 0.1450 | 0.6898 | -1.44 | Neutral | 0.213 | Benign | 0.050 | Benign | 4.04 | Benign | 0.02 | Affected | 3.61 | 5 | 0 | 0 | 2.4 | 28.05 | ||||||||||||||||||||||||||||||
| c.3916A>C | N1306H 2D AIThe SynGAP1 missense variant N1306H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “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 for this variant, 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 | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -2.949 | Likely Benign | 0.159 | Likely Benign | Likely Benign | 0.240 | Likely Benign | 0.1705 | 0.7846 | -3.42 | Deleterious | 0.961 | Probably Damaging | 0.825 | Possibly Damaging | 2.54 | Benign | 0.00 | Affected | 2 | 1 | 0.3 | 23.04 | |||||||||||||||||||||||||||||||||||
| c.3916A>G | N1306D 2D AIThe SynGAP1 missense variant N1306D is not 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, 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 does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -2.089 | Likely Benign | 0.207 | Likely Benign | Likely Benign | 0.143 | Likely Benign | 0.2018 | 0.4992 | -3.43 | Deleterious | 0.001 | Benign | 0.010 | Benign | 2.58 | Benign | 0.00 | Affected | 2 | 1 | 0.0 | 0.98 | |||||||||||||||||||||||||||||||||||
| c.3916A>T | N1306Y 2D AIThe SynGAP1 missense variant N1306Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact for the variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -4.193 | Likely Benign | 0.298 | Likely Benign | Likely Benign | 0.273 | Likely Benign | 0.0732 | 0.6658 | -5.59 | Deleterious | 0.961 | Probably Damaging | 0.825 | Possibly Damaging | 2.54 | Benign | 0.00 | Affected | -2 | -2 | 2.2 | 49.07 | |||||||||||||||||||||||||||||||||||
| c.3917A>C | N1306T 2D AIThe SynGAP1 missense variant N1306T is reported in gnomAD (ID 6‑33451791‑A‑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, 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 not available for this variant. Overall, the majority of evidence points to a benign impact, 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 | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | 6-33451791-A-C | -1.863 | Likely Benign | 0.156 | Likely Benign | Likely Benign | 0.240 | Likely Benign | 0.1588 | 0.8327 | -4.17 | Deleterious | 0.697 | Possibly Damaging | 0.399 | Benign | 2.59 | Benign | 0.00 | Affected | 3.77 | 5 | 0 | 0 | 2.8 | -13.00 | ||||||||||||||||||||||||||||||||
| c.3917A>G | N1306S 2D AIThe SynGAP1 missense variant N1306S is not 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, SGM‑Consensus as likely benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -1.344 | Likely Benign | 0.083 | Likely Benign | Likely Benign | 0.233 | Likely Benign | 0.4120 | 0.7826 | -3.49 | Deleterious | 0.319 | Benign | 0.242 | Benign | 2.69 | Benign | 0.00 | Affected | 1 | 1 | 2.7 | -27.03 | |||||||||||||||||||||||||||||||||||
| c.3917A>T | N1306I 2D AIThe SynGAP1 missense variant N1306I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -3.234 | Likely Benign | 0.296 | Likely Benign | Likely Benign | 0.188 | Likely Benign | 0.0837 | 0.6672 | -6.15 | Deleterious | 0.890 | Possibly Damaging | 0.761 | Possibly Damaging | 2.56 | Benign | 0.00 | Affected | -2 | -3 | 8.0 | -0.94 | |||||||||||||||||||||||||||||||||||
| c.3918C>A | N1306K 2D AIThe SynGAP1 missense variant N1306K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -3.021 | Likely Benign | 0.585 | Likely Pathogenic | Likely Benign | 0.140 | Likely Benign | 0.2375 | 0.6234 | -4.00 | Deleterious | 0.532 | Possibly Damaging | 0.327 | Benign | 2.61 | Benign | 0.00 | Affected | 1 | 0 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||||||||
| c.3918C>G | N1306K 2D AIThe SynGAP1 missense variant N1306K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.795062 | Disordered | 0.902190 | Binding | 0.367 | 0.888 | 0.875 | -3.021 | Likely Benign | 0.585 | Likely Pathogenic | Likely Benign | 0.177 | Likely Benign | 0.2375 | 0.6234 | -4.00 | Deleterious | 0.532 | Possibly Damaging | 0.327 | Benign | 2.61 | Benign | 0.00 | Affected | 1 | 0 | -0.4 | 14.07 | ||||||||||||||||||||||||||||||||||||
| c.2341A>C | M781L 2D AIThe SynGAP1 missense variant M781L is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | -2.334 | Likely Benign | 0.140 | Likely Benign | Likely Benign | 0.143 | Likely Benign | 0.1530 | 0.3669 | -0.41 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.83 | Benign | 0.88 | Tolerated | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.2341A>G | M781V 2D AIThe SynGAP1 missense variant M781V is catalogued in gnomAD (ID 6‑33442893‑A‑G) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool examined—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No 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, was not available for this variant. Overall, the evidence overwhelmingly supports a benign effect, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | 6-33442893-A-G | 4 | 2.48e-6 | -2.624 | Likely Benign | 0.068 | Likely Benign | Likely Benign | 0.174 | Likely Benign | 0.3081 | 0.2705 | 0.00 | Neutral | 0.000 | Benign | 0.001 | Benign | 3.03 | Benign | 0.90 | Tolerated | 3.64 | 6 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||||||||||
| c.2341A>T | M781L 2D AIThe SynGAP1 missense variant M781L is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this benign classification: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this prediction is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | -2.334 | Likely Benign | 0.140 | Likely Benign | Likely Benign | 0.143 | Likely Benign | 0.1530 | 0.3669 | -0.41 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.83 | Benign | 0.88 | Tolerated | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.2342T>A | M781K 2D AIThe SynGAP1 missense variant M781K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | -6.321 | Likely Benign | 0.734 | Likely Pathogenic | Likely Benign | 0.258 | Likely Benign | 0.1550 | 0.0688 | -1.47 | Neutral | 0.138 | Benign | 0.150 | Benign | 2.72 | Benign | 0.20 | Tolerated | 0 | -1 | -5.8 | -3.02 | |||||||||||||||||||||||||||||||||||
| c.2342T>C | M781T 2D AIThe SynGAP1 missense variant M781T is catalogued in gnomAD (ID 6‑33442894‑T‑C) and has no ClinVar entry. Across the evaluated in‑silico tools, every predictor classifies the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool reports a pathogenic or likely pathogenic outcome. The high‑accuracy consensus methods reinforce this view: 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. Based on the unanimous benign predictions and the lack of any 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 | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | 6-33442894-T-C | 1 | 6.21e-7 | -3.774 | Likely Benign | 0.310 | Likely Benign | Likely Benign | 0.175 | Likely Benign | 0.2267 | 0.1599 | -0.86 | Neutral | 0.015 | Benign | 0.037 | Benign | 2.75 | Benign | 0.59 | Tolerated | 3.64 | 6 | -1 | -1 | -2.6 | -30.09 | ||||||||||||||||||||||||||||||
| c.2342T>G | M781R 2D AIThe SynGAP1 missense variant M781R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | -4.990 | Likely Benign | 0.697 | Likely Pathogenic | Likely Benign | 0.265 | Likely Benign | 0.1685 | 0.0837 | -1.72 | Neutral | 0.327 | Benign | 0.206 | Benign | 2.71 | Benign | 0.14 | Tolerated | 0 | -1 | -6.4 | 24.99 | |||||||||||||||||||||||||||||||||||
| c.2343G>A | M781I 2D AIThe SynGAP1 missense variant M781I is listed in ClinVar (ID 2802065.0) as Benign and is not reported in gnomAD. All available in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions strongly support a benign effect, consistent with the ClinVar designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | Benign | 1 | -2.484 | Likely Benign | 0.323 | Likely Benign | Likely Benign | 0.101 | Likely Benign | 0.1405 | 0.2793 | 0.05 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.89 | Benign | 1.00 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||
| c.2343G>C | M781I 2D AIThe SynGAP1 missense variant M781I is catalogued in gnomAD (ID 6‑33442895‑G‑C) but has no ClinVar entry. 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 is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its status is unavailable. Overall, the consensus of all available predictions is benign, 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 | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | 6-33442895-G-C | 1 | 6.21e-7 | -2.484 | Likely Benign | 0.323 | Likely Benign | Likely Benign | 0.101 | Likely Benign | 0.1405 | 0.2793 | 0.05 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.89 | Benign | 1.00 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | ||||||||||||||||||||||||||||||
| c.2343G>T | M781I 2D AIThe SynGAP1 missense variant M781I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the evidence strongly suggests that M781I is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.580690 | Disordered | 0.792850 | Binding | 0.342 | 0.889 | 0.625 | -2.484 | Likely Benign | 0.323 | Likely Benign | Likely Benign | 0.101 | Likely Benign | 0.1405 | 0.2793 | 0.05 | Neutral | 0.000 | Benign | 0.001 | Benign | 2.89 | Benign | 1.00 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||
| c.2347A>C | M783L 2D AIThe SynGAP1 missense variant M783L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the collective evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -1.915 | Likely Benign | 0.138 | Likely Benign | Likely Benign | 0.108 | Likely Benign | 0.1727 | 0.4461 | -0.48 | Neutral | 0.004 | Benign | 0.006 | Benign | 2.99 | Benign | 1.00 | Tolerated | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.2347A>G | M783V 2D AIThe SynGAP1 missense variant M783V is catalogued in gnomAD (ID 6‑33442899‑A‑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 reports a pathogenic outcome. 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. Consequently, the variant is most likely benign, and this prediction 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 | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | 6-33442899-A-G | 1 | 6.21e-7 | -3.453 | Likely Benign | 0.086 | Likely Benign | Likely Benign | 0.065 | Likely Benign | 0.3444 | 0.3710 | -0.96 | Neutral | 0.072 | Benign | 0.026 | Benign | 2.85 | Benign | 0.12 | Tolerated | 3.64 | 6 | 1 | 2 | 2.3 | -32.06 | ||||||||||||||||||||||||||||||
| c.2347A>T | M783L 2D AIThe SynGAP1 missense variant M783L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the change as benign. No tool in the dataset predicts pathogenicity. High‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability approach, has no available result for this variant. Overall, the collective evidence strongly supports a benign interpretation, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -1.915 | Likely Benign | 0.138 | Likely Benign | Likely Benign | 0.110 | Likely Benign | 0.1727 | 0.4461 | -0.48 | Neutral | 0.004 | Benign | 0.006 | Benign | 2.99 | Benign | 1.00 | Tolerated | 4 | 2 | 1.9 | -18.03 | |||||||||||||||||||||||||||||||||||
| c.2348T>A | M783K 2D AIThe SynGAP1 missense variant M783K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -4.923 | Likely Benign | 0.693 | Likely Pathogenic | Likely Benign | 0.206 | Likely Benign | 0.1730 | 0.0912 | -2.70 | Deleterious | 0.925 | Possibly Damaging | 0.424 | Benign | 2.66 | Benign | 0.01 | Affected | 0 | -1 | -5.8 | -3.02 | ||||||||||||||||||||||||||||||||||||
| c.2348T>C | M783T 2D AIThe SynGAP1 missense variant M783T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the high‑accuracy consensus points to a benign effect, with no conflict with ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -4.064 | Likely Benign | 0.299 | Likely Benign | Likely Benign | 0.111 | Likely Benign | 0.2217 | 0.2308 | -2.08 | Neutral | 0.625 | Possibly Damaging | 0.265 | Benign | 2.69 | Benign | 0.03 | Affected | -1 | -1 | -2.6 | -30.09 | |||||||||||||||||||||||||||||||||||
| c.2348T>G | M783R 2D AIThe SynGAP1 missense variant M783R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -3.849 | Likely Benign | 0.655 | Likely Pathogenic | Likely Benign | 0.208 | Likely Benign | 0.1815 | 0.0893 | -2.69 | Deleterious | 0.925 | Possibly Damaging | 0.529 | Possibly Damaging | 2.66 | Benign | 0.01 | Affected | 0 | -1 | -6.4 | 24.99 | ||||||||||||||||||||||||||||||||||||
| c.2349G>A | M783I 2D AIThe SynGAP1 missense variant M783I is listed in ClinVar as a benign alteration (ClinVar ID 3618151.0) and is present in the gnomAD database (gnomAD ID 6‑33442901‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a likely benign effect. The Foldetta protein‑folding stability analysis is not available for this variant. Overall, the computational evidence strongly suggests that the variant is most likely benign, in agreement with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | Benign | 1 | 6-33442901-G-A | 6 | 3.72e-6 | -3.560 | Likely Benign | 0.418 | Ambiguous | Likely Benign | 0.042 | Likely Benign | 0.1540 | 0.3710 | -0.54 | Neutral | 0.004 | Benign | 0.006 | Benign | 2.87 | Benign | 0.22 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | ||||||||||||||||||||||||||||
| c.2349G>C | M783I 2D AIThe SynGAP1 missense variant M783I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Consensus from multiple in‑silico predictors classifies the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all return benign scores, and AlphaMissense‑Optimized also predicts a benign effect. No tool in the set indicates pathogenicity. The high‑accuracy assessments corroborate this view: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and Foldetta data are unavailable. Consequently, the aggregate evidence strongly supports a benign interpretation for M783I, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -3.560 | Likely Benign | 0.418 | Ambiguous | Likely Benign | 0.042 | Likely Benign | 0.1540 | 0.3710 | -0.54 | Neutral | 0.004 | Benign | 0.006 | Benign | 2.87 | Benign | 0.22 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||
| c.2349G>T | M783I 2D AIThe SynGAP1 missense variant M783I is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect. Benign calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the computational evidence strongly supports a benign classification for M783I, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.736850 | Disordered | 0.738119 | Binding | 0.331 | 0.889 | 0.625 | -3.560 | Likely Benign | 0.418 | Ambiguous | Likely Benign | 0.042 | Likely Benign | 0.1540 | 0.3710 | -0.54 | Neutral | 0.004 | Benign | 0.006 | Benign | 2.87 | Benign | 0.22 | Tolerated | 3.64 | 6 | 1 | 2 | 2.6 | -18.03 | |||||||||||||||||||||||||||||||||
| c.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 | 0.2368 | 0.3009 | -1.07 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 4.19 | Benign | 0.06 | Tolerated | 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 | 0.2447 | 0.3876 | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 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 | 0.2260 | 0.3176 | -1.03 | Neutral | 0.925 | Possibly Damaging | 0.629 | Possibly Damaging | 4.21 | Benign | 0.04 | Affected | -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 | 0.1451 | 0.2843 | -0.26 | Neutral | 0.451 | Benign | 0.285 | Benign | 4.18 | Benign | 0.06 | Tolerated | 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 | 0.4397 | 0.0384 | -0.05 | Neutral | 0.451 | Benign | 0.220 | Benign | 4.23 | Benign | 0.01 | Affected | -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 | 0.2646 | 0.2179 | -0.94 | Neutral | 0.994 | Probably Damaging | 0.888 | Possibly Damaging | 4.15 | Benign | 0.00 | Affected | -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 | 0.2447 | 0.3876 | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 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 | 0.2447 | 0.3876 | -1.00 | Neutral | 0.625 | Possibly Damaging | 0.430 | Benign | 4.22 | Benign | 0.73 | Tolerated | 4.32 | 2 | 2 | 0 | 1.0 | -34.02 | |||||||||||||||||||||||||||||||||
| c.2947A>C | S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and also indicates a likely pathogenic outcome. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for S983R, and this conclusion does not contradict any ClinVar annotation, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -4.733 | Likely Benign | 0.992 | Likely Pathogenic | Likely Pathogenic | 0.156 | Likely Benign | 0.1163 | 0.3740 | -2.66 | Deleterious | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.03 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2947A>G | S983G 2D AIThe SynGAP1 missense variant S983G is not 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). High‑accuracy methods show AlphaMissense‑Optimized as benign; the SGM Consensus is unavailable, and Foldetta results are not provided, so no folding‑stability evidence is available. Overall, the balance of evidence (five pathogenic vs four benign predictions) suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -5.206 | Likely Benign | 0.638 | Likely Pathogenic | Likely Benign | 0.109 | Likely Benign | 0.2521 | 0.4480 | -2.22 | Neutral | 0.979 | Probably Damaging | 0.982 | Probably Damaging | 2.17 | Pathogenic | 0.00 | Affected | 1 | 0 | 0.4 | -30.03 | ||||||||||||||||||||||||||||||||||||
| c.2947A>T | S983C 2D AIThe SynGAP1 missense variant S983C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -7.083 | In-Between | 0.741 | Likely Pathogenic | Likely Benign | 0.162 | Likely Benign | 0.1657 | 0.5298 | -2.64 | Deleterious | 0.999 | Probably Damaging | 0.997 | Probably Damaging | 2.02 | Pathogenic | 0.00 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2948G>A | S983N 2D AISynGAP1 missense variant S983N is listed as Benign in ClinVar (ID 469153) and is present in gnomAD (6‑33443500‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive; Foldetta results are not available. Overall, the majority of available predictions (five pathogenic vs. three benign) suggest a pathogenic impact, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | Likely Benign | 1 | 6-33443500-G-A | 6 | 3.72e-6 | -5.604 | Likely Benign | 0.909 | Likely Pathogenic | Ambiguous | 0.136 | Likely Benign | 0.1933 | 0.4069 | -1.78 | Neutral | 0.991 | Probably Damaging | 0.988 | Probably Damaging | 2.04 | Pathogenic | 0.00 | Affected | 4.32 | 1 | 1 | 1 | -2.7 | 27.03 | |||||||||||||||||||||||||||||
| c.2948G>C | S983T 2D AIThe SynGAP1 missense variant S983T is not 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Overall, the balance of evidence leans toward pathogenicity, with five tools supporting a deleterious effect versus four supporting benign. This prediction 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. | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -4.493 | Likely Benign | 0.588 | Likely Pathogenic | Likely Benign | 0.172 | Likely Benign | 0.2042 | 0.5517 | -1.65 | Neutral | 0.979 | Probably Damaging | 0.982 | Probably Damaging | 2.08 | Pathogenic | 0.00 | Affected | 1 | 1 | 0.1 | 14.03 | ||||||||||||||||||||||||||||||||||||
| c.2948G>T | S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -6.259 | Likely Benign | 0.968 | Likely Pathogenic | Likely Pathogenic | 0.190 | Likely Benign | 0.1380 | 0.4625 | -2.67 | Deleterious | 0.997 | Probably Damaging | 0.996 | Probably Damaging | 2.02 | Pathogenic | 0.00 | Affected | -1 | -2 | 5.3 | 26.08 | |||||||||||||||||||||||||||||||||||
| c.2949C>A | S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, 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 (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -4.733 | Likely Benign | 0.992 | Likely Pathogenic | Likely Pathogenic | 0.190 | Likely Benign | 0.1163 | 0.3740 | -2.66 | Deleterious | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.03 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| c.2949C>G | S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, 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 (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Pathogenic | 0.707965 | Disordered | 0.960212 | Binding | 0.277 | 0.889 | 0.625 | -4.733 | Likely Benign | 0.992 | Likely Pathogenic | Likely Pathogenic | 0.190 | Likely Benign | 0.1163 | 0.3740 | -2.66 | Deleterious | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.03 | Pathogenic | 0.00 | Affected | 0 | -1 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||||
| 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 | 0.1546 | 0.6793 | -2.14 | Neutral | 0.025 | Benign | 0.012 | Benign | 4.11 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.3164 | 0.5784 | -2.54 | Deleterious | 0.649 | Possibly Damaging | 0.157 | Benign | 4.05 | Benign | 0.35 | Tolerated | 3.77 | 5 | -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 | 0.3102 | 0.6215 | -2.24 | Neutral | 0.481 | Possibly Damaging | 0.157 | Benign | 4.03 | Benign | 0.03 | Affected | 3.77 | 5 | -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 | 0.1751 | 0.5523 | -3.16 | Deleterious | 0.997 | Probably Damaging | 0.840 | Possibly Damaging | 3.96 | Benign | 0.00 | Affected | 3.77 | 5 | -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 | 0.1370 | 0.4153 | -2.87 | Deleterious | 0.970 | Probably Damaging | 0.637 | Possibly Damaging | 3.99 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.2218 | 0.6470 | -3.33 | Deleterious | 0.649 | Possibly Damaging | 0.157 | Benign | 4.00 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.1190 | 0.4502 | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.2541 | 0.5170 | -1.83 | Neutral | 0.979 | Probably Damaging | 0.973 | Probably Damaging | 2.63 | Benign | 0.03 | Affected | 3.77 | 5 | 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 | 0.1571 | 0.6166 | -2.33 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.59 | Benign | 0.01 | Affected | 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 | 0.1940 | 0.5197 | -1.25 | Neutral | 0.991 | Probably Damaging | 0.982 | Probably Damaging | 2.69 | Benign | 0.02 | Affected | 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 | 0.2048 | 0.6514 | -1.32 | Neutral | 0.979 | Probably Damaging | 0.973 | Probably Damaging | 2.71 | Benign | 0.04 | Affected | 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 | 0.1322 | 0.5712 | -2.05 | Neutral | 0.997 | Probably Damaging | 0.995 | Probably Damaging | 2.62 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.1190 | 0.4502 | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | -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 | 0.1190 | 0.4502 | -1.96 | Neutral | 0.999 | Probably Damaging | 0.996 | Probably Damaging | 2.72 | Benign | 0.01 | Affected | 3.77 | 5 | -1 | 0 | -3.7 | 69.11 | |||||||||||||||||||||||||||||||||
| 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 | 0.1073 | 0.3911 | -0.66 | Neutral | 0.186 | Benign | 0.055 | Benign | 2.55 | Benign | 0.13 | Tolerated | 3.77 | 5 | 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 | 0.1560 | 0.3561 | -0.62 | Neutral | 0.779 | Possibly Damaging | 0.211 | Benign | 2.57 | Benign | 0.08 | Tolerated | 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 | 0.1192 | 0.1514 | -1.32 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.47 | Pathogenic | 0.02 | Affected | -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 | 0.3199 | 0.1918 | -1.25 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.45 | Pathogenic | 0.04 | Affected | 3.77 | 5 | -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 | 0.1274 | 0.1357 | -1.51 | Neutral | 0.997 | Probably Damaging | 0.939 | Probably Damaging | 2.47 | Pathogenic | 0.02 | Affected | -3 | -2 | -8.3 | 43.03 | ||||||||||||||||||||||||||||||||||||
| c.3403A>C | K1135Q 2D AIThe SynGAP1 missense variant K1135Q has no ClinVar entry and is not reported in gnomAD. 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, 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 | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | -4.622 | Likely Benign | 0.566 | Likely Pathogenic | Likely Benign | 0.171 | Likely Benign | 0.5016 | 0.1356 | Weaken | -0.66 | Neutral | 0.099 | Benign | 0.150 | Benign | 5.43 | Benign | 0.07 | Tolerated | 1 | 1 | 0.4 | -0.04 | ||||||||||||||||||||||||||||||||||
| c.3403A>G | K1135E 2D AIThe SynGAP1 missense variant K1135E is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443955‑A‑G). 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta) results are unavailable. Overall, the preponderance of evidence points to a benign impact for K1135E, 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. | Likely Benign | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | 6-33443955-A-G | -6.499 | Likely Benign | 0.924 | Likely Pathogenic | Ambiguous | 0.239 | Likely Benign | 0.4330 | 0.1476 | -0.76 | Neutral | 0.224 | Benign | 0.237 | Benign | 5.45 | Benign | 0.12 | Tolerated | 4.32 | 2 | 1 | 0 | 0.4 | 0.94 | ||||||||||||||||||||||||||||||||
| c.3404A>C | K1135T 2D AIThe SynGAP1 missense variant K1135T is listed in ClinVar (ID 1166087.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443956‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | Conflicting | 2 | 6-33443956-A-C | 1 | 6.75e-7 | -4.778 | Likely Benign | 0.779 | Likely Pathogenic | Likely Benign | 0.210 | Likely Benign | 0.2544 | 0.3521 | -0.90 | Neutral | 0.411 | Benign | 0.321 | Benign | 5.46 | Benign | 0.10 | Tolerated | 4.32 | 2 | 0 | -1 | 3.2 | -27.07 | ||||||||||||||||||||||||||||
| c.3404A>G | K1135R 2D AIThe SynGAP1 missense variant K1135R 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 K1135R, 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 | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | -2.286 | Likely Benign | 0.122 | Likely Benign | Likely Benign | 0.209 | Likely Benign | 0.5095 | 0.1674 | Weaken | -0.82 | Neutral | 0.586 | Possibly Damaging | 0.321 | Benign | 5.44 | Benign | 0.15 | Tolerated | 3 | 2 | -0.6 | 28.01 | ||||||||||||||||||||||||||||||||||
| c.3404A>T | K1135M 2D AIThe SynGAP1 K1135M 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 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 (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence leans toward a benign interpretation, 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 | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | -5.953 | Likely Benign | 0.931 | Likely Pathogenic | Ambiguous | 0.423 | Likely Benign | 0.1669 | 0.4164 | -1.65 | Neutral | 0.938 | Possibly Damaging | 0.819 | Possibly Damaging | 5.42 | Benign | 0.02 | Affected | 0 | -1 | 5.8 | 3.02 | |||||||||||||||||||||||||||||||||||
| c.3405G>C | K1135N 2D AIThe SynGAP1 missense variant K1135N is listed in ClinVar (ID 633521.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. In contrast, AlphaMissense‑Default and AlphaMissense‑Optimized both predict a pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions support a benign classification, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | Uncertain | 1 | -5.715 | Likely Benign | 0.960 | Likely Pathogenic | Likely Pathogenic | 0.166 | Likely Benign | 0.4152 | 0.1793 | -0.97 | Neutral | 0.411 | Benign | 0.321 | Benign | 5.43 | Benign | 0.07 | Tolerated | 4.32 | 2 | 1 | 0 | 0.4 | -14.07 | |||||||||||||||||||||||||||||||
| c.3405G>T | K1135N 2D AIThe SynGAP1 missense variant K1135N is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443957‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign interpretation. This consensus does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.887230 | Disordered | 0.790969 | Binding | 0.303 | 0.889 | 0.875 | 6-33443957-G-T | -5.715 | Likely Benign | 0.960 | Likely Pathogenic | Likely Pathogenic | 0.166 | Likely Benign | 0.4152 | 0.1793 | -0.97 | Neutral | 0.411 | Benign | 0.321 | Benign | 5.43 | Benign | 0.07 | Tolerated | 4.32 | 2 | 1 | 0 | 0.4 | -14.07 | ||||||||||||||||||||||||||||||||
| 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 | 0.4317 | 0.0384 | 1.31 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.37 | Benign | 0.91 | Tolerated | 3.77 | 5 | 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 | 0.4317 | 0.0384 | 1.31 | Neutral | 0.000 | Benign | 0.001 | Benign | 4.37 | Benign | 0.91 | Tolerated | 3.77 | 5 | 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 | 0.4126 | 0.1745 | -1.36 | Neutral | 0.208 | Benign | 0.077 | Benign | 4.21 | Benign | 0.12 | Tolerated | -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 | 0.3974 | 0.1211 | -0.79 | Neutral | 0.115 | Benign | 0.057 | Benign | 4.26 | Benign | 0.13 | Tolerated | -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 | 0.2256 | 0.3338 | -0.65 | Neutral | 0.115 | Benign | 0.057 | Benign | 4.29 | Benign | 0.16 | Tolerated | -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 | 0.3427 | 0.1929 | -1.54 | Neutral | 0.872 | Possibly Damaging | 0.468 | Possibly Damaging | 4.21 | Benign | 0.02 | Affected | -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 | 0.3427 | 0.1929 | -1.54 | Neutral | 0.872 | Possibly Damaging | 0.468 | Possibly Damaging | 4.21 | Benign | 0.02 | Affected | -8 | -2 | 3.4 | -83.07 | |||||||||||||||||||||||||||||||||||
| c.2335A>C | S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -4.044 | Likely Benign | 0.950 | Likely Pathogenic | Ambiguous | 0.103 | Likely Benign | 0.0961 | 0.4046 | -0.74 | Neutral | 0.846 | Possibly Damaging | 0.627 | Possibly Damaging | 2.29 | Pathogenic | 0.12 | Tolerated | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.2335A>G | S779G 2D AIThe SynGAP1 missense variant S779G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -4.304 | Likely Benign | 0.111 | Likely Benign | Likely Benign | 0.103 | Likely Benign | 0.2894 | 0.5087 | 0.38 | Neutral | 0.393 | Benign | 0.324 | Benign | 2.65 | Benign | 0.53 | Tolerated | 1 | 0 | 0.4 | -30.03 | |||||||||||||||||||||||||||||||||||
| c.2335A>T | S779C 2D AIThe SynGAP1 missense variant S779C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -6.375 | Likely Benign | 0.196 | Likely Benign | Likely Benign | 0.230 | Likely Benign | 0.1177 | 0.6350 | -1.88 | Neutral | 0.992 | Probably Damaging | 0.905 | Possibly Damaging | 2.28 | Pathogenic | 0.05 | Affected | 0 | -1 | 3.3 | 16.06 | |||||||||||||||||||||||||||||||||||
| c.2336G>A | S779N 2D AIThe SynGAP1 missense variant S779N is listed in gnomAD (ID 6‑33442494‑G‑A) but has no ClinVar entry. Functional 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. A high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a benign majority. The AlphaMissense‑Optimized score is benign, and no Foldetta stability assessment is available. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | 6-33442494-G-A | -4.880 | Likely Benign | 0.384 | Ambiguous | Likely Benign | 0.087 | Likely Benign | 0.1327 | 0.4984 | -0.75 | Neutral | 0.021 | Benign | 0.026 | Benign | 2.30 | Pathogenic | 0.23 | Tolerated | 3.64 | 6 | 1 | 1 | -2.7 | 27.03 | |||||||||||||||||||||||||||||||||
| c.2336G>C | S779T 2D AIThe SynGAP1 missense variant S779T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. Only two tools—polyPhen‑2 HumDiv and FATHMM—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are not available for this variant. Overall, the consensus of available predictions points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -4.458 | Likely Benign | 0.144 | Likely Benign | Likely Benign | 0.132 | Likely Benign | 0.1491 | 0.6392 | -0.71 | Neutral | 0.611 | Possibly Damaging | 0.396 | Benign | 2.34 | Pathogenic | 0.79 | Tolerated | 1 | 1 | 0.1 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.2336G>T | S779I 2D AIThe SynGAP1 missense variant S779I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy methods give a benign call from AlphaMissense‑Optimized; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -6.261 | Likely Benign | 0.578 | Likely Pathogenic | Likely Benign | 0.198 | Likely Benign | 0.1046 | 0.6248 | -2.10 | Neutral | 0.918 | Possibly Damaging | 0.827 | Possibly Damaging | 2.28 | Pathogenic | 0.05 | Affected | -1 | -2 | 5.3 | 26.08 | ||||||||||||||||||||||||||||||||||||
| c.2337C>A | S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -4.044 | Likely Benign | 0.950 | Likely Pathogenic | Ambiguous | 0.119 | Likely Benign | 0.0961 | 0.4046 | -0.74 | Neutral | 0.846 | Possibly Damaging | 0.627 | Possibly Damaging | 2.29 | Pathogenic | 0.12 | Tolerated | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.2337C>G | S779R 2D AIThe SynGAP1 missense variant S779R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.509769 | Disordered | 0.834974 | Binding | 0.321 | 0.890 | 0.375 | -4.044 | Likely Benign | 0.950 | Likely Pathogenic | Ambiguous | 0.124 | Likely Benign | 0.0961 | 0.4046 | -0.74 | Neutral | 0.846 | Possibly Damaging | 0.627 | Possibly Damaging | 2.29 | Pathogenic | 0.12 | Tolerated | 0 | -1 | -3.7 | 69.11 | ||||||||||||||||||||||||||||||||||||
| c.244C>A | L82M 2D AIThe SynGAP1 missense variant L82M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized prediction is uncertain, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.637480 | Disordered | 0.517720 | Binding | 0.284 | 0.890 | 0.375 | -4.608 | Likely Benign | 0.888 | Likely Pathogenic | Ambiguous | 0.082 | Likely Benign | 0.0744 | 0.3278 | -0.68 | Neutral | 0.939 | Possibly Damaging | 0.114 | Benign | 3.67 | Benign | 0.00 | Affected | 4 | 2 | -1.9 | 18.03 | |||||||||||||||||||||||||||||||||||
| c.244C>G | L82V 2D AIThe SynGAP1 missense variant L82V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33425852‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore indicate a benign likelihood: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.637480 | Disordered | 0.517720 | Binding | 0.284 | 0.890 | 0.375 | 6-33425852-C-G | -6.701 | Likely Benign | 0.914 | Likely Pathogenic | Ambiguous | 0.065 | Likely Benign | 0.1467 | 0.2353 | -1.13 | Neutral | 0.371 | Benign | 0.024 | Benign | 3.72 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 2 | 0.4 | -14.03 | ||||||||||||||||||||||||||||||||
| c.245T>A | L82Q 2D AIThe SynGAP1 missense variant L82Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign prediction. Foldetta results are unavailable. Overall, the majority of conventional tools lean toward benign, and the SGM Consensus supports this, but the AlphaMissense‑Optimized prediction introduces a pathogenic signal. Consequently, the variant is most likely benign based on the prevailing evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.637480 | Disordered | 0.517720 | Binding | 0.284 | 0.890 | 0.375 | -7.576 | In-Between | 0.987 | Likely Pathogenic | Likely Pathogenic | 0.079 | Likely Benign | 0.1150 | 0.0790 | -2.16 | Neutral | 0.939 | Possibly Damaging | 0.114 | Benign | 3.71 | Benign | 0.00 | Affected | -2 | -2 | -7.3 | 14.97 | ||||||||||||||||||||||||||||||||||||
| c.245T>C | L82P 2D AIThe SynGAP1 missense variant L82P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33425853‑T‑C). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.637480 | Disordered | 0.517720 | Binding | 0.284 | 0.890 | 0.375 | 6-33425853-T-C | 1 | 6.20e-7 | -7.667 | In-Between | 0.991 | Likely Pathogenic | Likely Pathogenic | 0.125 | Likely Benign | 0.3477 | 0.1118 | -2.73 | Deleterious | 0.939 | Possibly Damaging | 0.162 | Benign | 3.64 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | -3 | -5.4 | -16.04 | |||||||||||||||||||||||||||||||
| c.245T>G | L82R 2D AIThe SynGAP1 missense variant L82R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, and this is not contradicted by any ClinVar annotation. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.637480 | Disordered | 0.517720 | Binding | 0.284 | 0.890 | 0.375 | -6.345 | Likely Benign | 0.974 | Likely Pathogenic | Likely Pathogenic | 0.077 | Likely Benign | 0.1338 | 0.0590 | -2.18 | Neutral | 0.939 | Possibly Damaging | 0.114 | Benign | 3.67 | Benign | 0.00 | Affected | -3 | -2 | -8.3 | 43.03 | |||||||||||||||||||||||||||||||||||
| 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 | 0.2047 | 0.4758 | -1.21 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.14 | Benign | 0.06 | Tolerated | 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 | 0.3821 | 0.4275 | -0.71 | Neutral | 0.000 | Benign | 0.002 | Benign | 4.19 | Benign | 0.18 | Tolerated | 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 | 0.3228 | 0.4366 | -0.57 | Neutral | 0.059 | Benign | 0.061 | Benign | 4.16 | Benign | 0.20 | Tolerated | 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 | 0.1379 | 0.4772 | -0.58 | Neutral | 0.586 | Possibly Damaging | 0.302 | Benign | 4.13 | Benign | 0.07 | Tolerated | 4.32 | 2 | 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 | 0.3228 | 0.4366 | -0.57 | Neutral | 0.059 | Benign | 0.061 | Benign | 4.16 | Benign | 0.20 | Tolerated | 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 | 0.1107 | 0.5198 | -1.66 | Neutral | 0.411 | Benign | 0.239 | Benign | 4.11 | Benign | 0.66 | Tolerated | 4.32 | 2 | 0 | -1 | 5.2 | 12.05 | ||||||||||||||||||||||||||||
| 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 | 0.0934 | 0.4415 | -3.13 | Deleterious | 0.896 | Possibly Damaging | 0.325 | Benign | 2.42 | Pathogenic | 0.01 | Affected | 3.77 | 5 | -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 | 0.0934 | 0.4415 | -3.13 | Deleterious | 0.896 | Possibly Damaging | 0.325 | Benign | 2.42 | Pathogenic | 0.01 | Affected | 3.77 | 5 | -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 | 0.0840 | 0.4610 | -3.45 | Deleterious | 1.000 | Probably Damaging | 0.988 | Probably Damaging | 2.37 | Pathogenic | 0.00 | Affected | -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 | 0.1460 | 0.4387 | -2.85 | Deleterious | 0.992 | Probably Damaging | 0.834 | Possibly Damaging | 2.59 | Benign | 0.01 | Affected | 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 | 0.3475 | 0.5331 | -1.73 | Neutral | 0.186 | Benign | 0.055 | Benign | 2.45 | Pathogenic | 0.02 | Affected | 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 | 0.1326 | 0.4413 | -2.81 | Deleterious | 0.984 | Probably Damaging | 0.722 | Possibly Damaging | 2.40 | Pathogenic | 0.00 | Affected | -1 | -3 | 4.6 | 42.08 | ||||||||||||||||||||||||||||||||||||
| 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 | 0.0919 | 0.4479 | -0.15 | Neutral | 0.986 | Probably Damaging | 0.875 | Possibly Damaging | 2.66 | Benign | 0.21 | Tolerated | 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 | 0.1658 | 0.3912 | -0.36 | Neutral | 0.051 | Benign | 0.037 | Benign | 2.79 | Benign | 0.37 | Tolerated | 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 | 0.3086 | 0.1119 | -0.42 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.68 | Benign | 0.25 | Tolerated | -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 | 0.0787 | 0.4033 | -2.00 | Neutral | 0.999 | Probably Damaging | 0.968 | Probably Damaging | 2.58 | Benign | 0.03 | Affected | -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 | 0.0772 | 0.4060 | -1.40 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.63 | Benign | 0.18 | Tolerated | 3.77 | 5 | 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 | 0.0772 | 0.4060 | -1.40 | Neutral | 0.986 | Probably Damaging | 0.823 | Possibly Damaging | 2.63 | Benign | 0.18 | Tolerated | 3.77 | 5 | 0 | 2 | -1.0 | 34.02 | |||||||||||||||||||||||||||||||||
| c.70G>A | V24I 2D AIThe SynGAP1 missense variant V24I is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6-33423479-G-A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the overwhelming majority of computational evidence supports a benign impact for V24I, and this conclusion does not contradict the ClinVar designation, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | Uncertain | 1 | 6-33423479-G-A | 9 | 5.58e-6 | -3.701 | Likely Benign | 0.137 | Likely Benign | Likely Benign | 0.069 | Likely Benign | 0.0844 | 0.4564 | -0.25 | Neutral | 0.043 | Benign | 0.031 | Benign | 3.96 | Benign | 0.00 | Affected | 4.32 | 1 | 3 | 4 | 0.3 | 14.03 | ||||||||||||||||||||||||||||
| c.70G>C | V24L 2D AIThe SynGAP1 missense variant V24L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for V24L, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | -2.590 | Likely Benign | 0.320 | Likely Benign | Likely Benign | 0.053 | Likely Benign | 0.1102 | 0.5226 | -0.62 | Neutral | 0.043 | Benign | 0.011 | Benign | 3.94 | Benign | 0.00 | Affected | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.70G>T | V24L 2D AIThe SynGAP1 missense variant V24L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for V24L, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | -2.590 | Likely Benign | 0.320 | Likely Benign | Likely Benign | 0.053 | Likely Benign | 0.1102 | 0.5226 | -0.62 | Neutral | 0.043 | Benign | 0.011 | Benign | 3.94 | Benign | 0.00 | Affected | 2 | 1 | -0.4 | 14.03 | |||||||||||||||||||||||||||||||||||
| c.71T>A | V24E 2D AIThe SynGAP1 missense variant V24E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, the SGM‑Consensus also indicates Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | -3.397 | Likely Benign | 0.517 | Ambiguous | Likely Benign | 0.171 | Likely Benign | 0.1133 | 0.2415 | -1.73 | Neutral | 0.198 | Benign | 0.074 | Benign | 3.77 | Benign | 0.00 | Affected | -2 | -2 | -7.7 | 29.98 | |||||||||||||||||||||||||||||||||||
| c.71T>C | V24A 2D AIThe SynGAP1 missense variant V24A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT predicts pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact for V24A. This prediction is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | -2.980 | Likely Benign | 0.299 | Likely Benign | Likely Benign | 0.074 | Likely Benign | 0.3117 | 0.3350 | -1.09 | Neutral | 0.000 | Benign | 0.001 | Benign | 3.83 | Benign | 0.00 | Affected | 0 | 0 | -2.4 | -28.05 | |||||||||||||||||||||||||||||||||||
| c.71T>G | V24G 2D AIThe SynGAP1 missense variant V24G is not reported in ClinVar (ClinVar status: not present) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | 0.541878 | Disordered | 0.438970 | Uncertain | 0.382 | 0.890 | 0.500 | -2.673 | Likely Benign | 0.256 | Likely Benign | Likely Benign | 0.178 | Likely Benign | 0.2081 | 0.3105 | -1.67 | Neutral | 0.026 | Benign | 0.049 | Benign | 3.77 | Benign | 0.00 | Affected | -1 | -3 | -4.6 | -42.08 | ||||||||||||||||||||||||||||||||||||
| c.73C>G | R25G 2D AIThe SynGAP1 missense variant R25G is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. When high‑accuracy tools are considered separately, AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome, and Foldetta data are unavailable. Overall, the majority of robust predictors lean toward a benign interpretation. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.461924 | Structured | 0.438941 | Uncertain | 0.373 | 0.890 | 0.375 | -3.533 | Likely Benign | 0.373 | Ambiguous | Likely Benign | 0.122 | Likely Benign | 0.3621 | 0.3572 | -1.69 | Neutral | 0.686 | Possibly Damaging | 0.630 | Possibly Damaging | 3.95 | Benign | 0.00 | Affected | -3 | -2 | 4.1 | -99.14 | |||||||||||||||||||||||||||||||||||
| c.73C>T | R25W 2D AIThe SynGAP1 missense variant R25W is listed in ClinVar with an “Uncertain” status (ClinVar ID 2993054.0) and is present in gnomAD (ID 6‑33423482‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review. | Likely Benign | 0.461924 | Structured | 0.438941 | Uncertain | 0.373 | 0.890 | 0.375 | Uncertain | 2 | 6-33423482-C-T | 6 | 3.72e-6 | -5.133 | Likely Benign | 0.549 | Ambiguous | Likely Benign | 0.158 | Likely Benign | 0.1224 | 0.3938 | -1.60 | Neutral | 0.994 | Probably Damaging | 0.919 | Probably Damaging | 3.92 | Benign | 0.00 | Affected | 4.32 | 1 | -3 | 2 | 3.6 | 30.03 | ||||||||||||||||||||||||||||
| c.74G>A | R25Q 2D AIThe SynGAP1 missense variant R25Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33423483‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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 | 0.461924 | Structured | 0.438941 | Uncertain | 0.373 | 0.890 | 0.375 | Uncertain | 1 | 6-33423483-G-A | 15 | 9.29e-6 | -4.126 | Likely Benign | 0.212 | Likely Benign | Likely Benign | 0.038 | Likely Benign | 0.3447 | 0.2566 | -0.70 | Neutral | 0.829 | Possibly Damaging | 0.614 | Possibly Damaging | 4.01 | Benign | 0.00 | Affected | 4.32 | 1 | 1 | 1 | 1.0 | -28.06 | ||||||||||||||||||||||||||||
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