SH2D1A (SH2 domain-containing protein 1A) variants and mutations
SH2D1A (also known as SH2 domain-containing protein 1A) is a human protein-coding gene encoding a SH2 domain-containing protein 1A protein. It coordinates signaling through SLAM-family immune receptors and is essential for normal T-cell and natural-killer-cell responses to Epstein-Barr virus. Loss-of-function variants cause X-linked lymphoproliferative disease type 1, with fulminant EBV-associated immune dysregulation. This analysis covers 299 SH2D1A variants and mutations. Of these, 90% have computational variant effect predictions. Disease context includes X-linked lymphoproliferative disease, lymphoma, and lymphoproliferative syndrome. Example SH2D1A variants include M1?, M1I, and M1T.
Variant analysis overview
- Gene: SH2D1A
- Protein: SH2 domain-containing protein 1A
- UniProt accession: O60880
- Organism: Homo sapiens
- Variants analyzed: 299
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 147 unspecified-consequence records; 40 synonymous variants; 96 missense variants; 6 stop-gained variants; 4 splice-region variants; 4 frameshift variants; 1 in-frame deletions; 1 stop lost
- Prediction scores: 269 variants have prediction scores (90% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: X-linked lymphoproliferative disease, lymphoma, lymphoproliferative syndrome, X-linked lymphoproliferative syndrome, hereditary disease, autoinflammatory syndrome, neurodegenerative disease, tropical spastic paraparesis, infection, systemic lupus erythematosus, tuberculosis, hepatocellular carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 1 post-translational modification sites.
- Structural context: 206 variants have structural context.
- PTM context: 1 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SH2D1A variants
Examples include M1?, M1I, M1T, M1V, D2G, D2D, A3S, A3T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, Variant assessed as somatic; high impact.
- M1I (p.Met1Ile), rs111033629, ClinGen CA255604, ClinVar RCV000011655, MetaLR 0.76, MetaSVM 0.53, Pathogenic
- M1T (p.Met1Thr), rs2147519353, ClinGen CA414122161, ClinVar RCV001946671, ClinVar RCV002264437, MetaLR 0.81, MetaSVM 0.77, Pathogenic/Likely pathogenic, X-linked lymphoproliferative disease due to SH2D1A deficiency; Autoinflammatory
- M1V (p.Met1Val), rs2522797198, ClinGen CA414122158, ClinVar RCV003150604, Pathogenic, X-linked lymphoproliferative disease due to SH2D1A deficiency
- D2G (p.Asp2Gly), rs1556619319, ClinGen CA414122169, ClinVar RCV000660264, ClinVar RCV000788711, AlphaMissense 0.30, MetaLR 0.51, Likely pathogenic, not provided; X-linked lymphoproliferative disease due to SH2D1A deficiency
- D2D (p.Asp2Asp), rs1298636213, gnomAD X-124346648-C-T, CADD 1.28
- A3S (p.Ala3Ser), rs148554414, ClinGen CA10509240, cosmic curated COSV63579, ClinVar RCV001520732, REVEL 0.60, MetaLR 0.69, Conflicting interpretations, not specified; X-linked lymphoproliferative disease due to SH2D1A deficiency; Au
- A3T (p.Ala3Thr), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, NCI-TCGA Cosmic COSV6357, REVEL 0.15, MetaLR 0.80, Variant assessed as somatic; moderate impact.
- V4V (p.Val4Val), rs142020430, gnomAD X-124346654-G-T, CADD 4.93
- A5T (p.Ala5Thr), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, Ensembl rs2147519386, MetaLR 0.78, MetaSVM 0.08, Variant assessed as somatic; moderate impact.
- A5S (p.Ala5Ser), gnomAD X-124346655-G-T, REVEL 0.23, MetaLR 0.65
- V6G (p.Val6Gly), ExAC rs755791045, gnomAD rs755791045, REVEL 0.89, MetaLR 0.96
- V6A (p.Val6Ala), gnomAD X-124346659-T-C, REVEL 0.81, MetaLR 0.95
- Y7C (p.Tyr7Cys), rs1569527111, ClinGen CA414122199, ClinVar RCV000781847, UniProt VAR 048005, AlphaMissense 0.92, MetaLR 0.99, Pathogenic, X-linked lymphoproliferative syndrome
- H8D (p.His8Asp), UniProt VAR 048006, Pathogenic, in XLP1
- H8P (p.His8Pro), rs2522797252, ClinGen CA414122208, ClinVar RCV003228222, Conflicting interpretations, X-linked lymphoproliferative disease due to SH2D1A deficiency
- H8Y (p.His8Tyr), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, MetaLR 0.96, MetaSVM 1.10, Variant assessed as somatic; moderate impact., in XLP1
- H8H (p.His8His), rs915605791, gnomAD X-124346666-T-C, CADD 1.13
- G9C (p.Gly9Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G9D (p.Gly9Asp), Ensembl rs2059993396, MetaLR 0.98, MetaSVM 1.03
- S12N (p.Ser12Asn), Ensembl rs2147519401, MetaLR 0.92, MetaSVM 0.95
- S12S (p.Ser12Ser), rs1259577571, gnomAD X-124346678-C-T, CADD 13.20
- R13K (p.Arg13Lys), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- R13R (p.Arg13Arg), rs1281416443, gnomAD X-124346681-G-A, CADD 8.08
- E14K (p.Glu14Lys), rs779822938, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, ExAC rs779822938, REVEL 0.55, MetaLR 0.56, Variant assessed as somatic; moderate impact.
- T15I (p.Thr15Ile), gnomAD X-124346686-C-T, REVEL 0.33, MetaLR 0.45
- T15T (p.Thr15Thr), rs2059993470, gnomAD X-124346687-C-T, CADD 0.56
- G16C (p.Gly16Cys), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, Variant assessed as somatic; moderate impact., in XLP1
- G16D (p.Gly16Asp), UniProt VAR 048007, MetaLR 0.96, MetaSVM 1.11, Pathogenic, in XLP1
- G16S (p.Gly16Ser), cosmic curated COSV63579, Ensembl rs2147519416, REVEL 0.67, MetaLR 0.90
- G16G (p.Gly16Gly), rs72610640, gnomAD X-124346690-C-T, CADD 6.79
- E17K (p.Glu17Lys), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, Ensembl rs2147519424, MetaLR 0.91, MetaSVM 1.05, Variant assessed as somatic; moderate impact.
- E17* (p.Glu17Ter), gnomAD X-124346691-G-T, CADD 36.00
- K18R (p.Lys18Arg), rs1303880423, ClinGen CA414122278, ClinVar RCV000727009, ClinVar RCV003509560, REVEL 0.20, MetaLR 0.38, Conflicting interpretations, not provided; X-linked lymphoproliferative disease due to SH2D1A deficiency
- K18K (p.Lys18Lys), rs778633764, gnomAD X-124346696-G-A, CADD 10.90
- K18N (p.Lys18Asn), gnomAD X-124346696-G-T, REVEL 0.38, MetaLR 0.58
- L19L (p.Leu19Leu), rs2059993558, gnomAD X-124346699-C-T, CADD 9.73
- L21R (p.Leu21Arg), rs2059993575, ClinGen CA414122297, ClinVar RCV001311403, Ensembl rs2059993575, AlphaMissense 0.38, MetaLR 0.46, Uncertain significance, not provided
- A22P (p.Ala22Pro), UniProt VAR 088139, Uncertain significance, in XLP1
- A22S (p.Ala22Ser), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, MetaLR 0.43, MetaSVM -0.38, Uncertain significance, in XLP1
- A22V (p.Ala22Val), gnomAD X-124346707-C-T, REVEL 0.37, MetaLR 0.54
- T23A (p.Thr23Ala), Ensembl rs2059993593
- T23S (p.Thr23Ser), Ensembl rs2059993593, MetaLR 0.30, MetaSVM -0.77
- T23I (p.Thr23Ile), gnomAD X-124346710-C-T, REVEL 0.28, MetaLR 0.41
- G24W (p.Gly24Trp), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, MetaLR 0.98, MetaSVM 1.07, Variant assessed as somatic; moderate impact.
- G24E (p.Gly24Glu), gnomAD X-124346713-G-A, REVEL 0.89, MetaLR 0.97
- L25M (p.Leu25Met), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, MetaLR 0.49, MetaSVM -0.34, Variant assessed as somatic; moderate impact.
- G27C (p.Gly27Cys), cosmic curated COSV63579, gnomAD rs1227385786
- G27S (p.Gly27Ser), UniProt VAR 048008, MetaLR 0.97, MetaSVM 1.09, Pathogenic, in XLP1
- G27G (p.Gly27Gly), gnomAD X-124346723-C-T, CADD 13.50
- S28R (p.Ser28Arg), UniProt VAR 048009, MetaLR 0.81, MetaSVM 0.76, Pathogenic, in XLP1
- S28S (p.Ser28Ser), rs748536692, gnomAD X-124346726-C-T, CADD 13.30
- Y29Y (p.Tyr29Tyr), gnomAD X-124346729-T-C, CADD 11.10
- L31P (p.Leu31Pro), UniProt VAR 048010, MetaLR 0.83, MetaSVM 0.82, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- L31L (p.Leu31Leu), rs2059993674, gnomAD X-124346733-C-T, CADD 13.00
- R32T (p.Arg32Thr), rs111033624, ClinGen CA255595, ClinVar RCV000011648, UniProt VAR 005612, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, X-linked lymphoproliferative disease due to SH2D1A deficiency
- R32R (p.Arg32Arg), rs2059993707, gnomAD X-124346738-G-A, CADD 12.10
- D33E (p.Asp33Glu), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, Variant assessed as somatic; moderate impact., in XLP1
- D33G (p.Asp33Gly), rs2059993731, ClinGen CA414122374, ClinVar RCV001091712, Ensembl rs2059993731, AlphaMissense 0.93, MetaLR 0.80, Uncertain significance, not provided
- D33Y (p.Asp33Tyr), UniProt VAR 048011, MetaLR 0.84, MetaSVM 0.88, Pathogenic, in XLP1
- S34R (p.Ser34Arg), Ensembl rs2059993746, MetaLR 0.90, MetaSVM 0.90, Conflicting interpretations, not provided; X-linked lymphoproliferative disease due to SH2D1A deficiency
- S34S (p.Ser34Ser), rs1484311033, gnomAD X-124346744-C-T, CADD 10.00
- E35* (p.Glu35Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E35D (p.Glu35Asp), NCI-TCGA Cosmic COSV6357, MetaLR 0.62, MetaSVM 0.11, Variant assessed as somatic; moderate impact.
- E35K (p.Glu35Lys), cosmic curated COSV10592, NCI-TCGA TCGA novel, Ensembl rs2147519489, REVEL 0.85, MetaLR 0.80, Variant assessed as somatic; moderate impact.
- S36N (p.Ser36Asn), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, MetaLR 0.91, MetaSVM 0.89, Variant assessed as somatic; moderate impact.
- S36T (p.Ser36Thr), gnomAD X-124346749-G-C, REVEL 0.46, MetaLR 0.84
- S36S (p.Ser36Ser), gnomAD X-124346750-C-T, CADD 8.32
- V37L (p.Val37Leu), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, REVEL 0.27, MetaLR 0.46, Variant assessed as somatic; moderate impact.
- V37M (p.Val37Met), cosmic curated COSV63578, TOPMed rs1484550706, gnomAD rs1484550706, REVEL 0.27, MetaLR 0.42, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- P38S (p.Pro38Ser), gnomAD rs1219670952, REVEL 0.48, MetaLR 0.65, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- P38T (p.Pro38Thr), NCI-TCGA TCGA novel, MetaLR 0.70, MetaSVM 0.55, Variant assessed as somatic; moderate impact.
- P38L (p.Pro38Leu), gnomAD X-124346755-C-T, REVEL 0.57, MetaLR 0.74
- P38Q (p.Pro38Gln), gnomAD X-124346755-C-A, REVEL 0.52, MetaLR 0.69
- P38H (p.Pro38His), gnomAD X-124365794-C-A, CADD 8.84, SIFT 0.02
- G39V (p.Gly39Val), rs1556619338, ClinGen CA414122418, ClinVar RCV000644910, Ensembl rs1556619338, CADD 23.10, SIFT 0.00, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- G39D (p.Gly39Asp), gnomAD X-124365761-G-A, CADD 20.30, SIFT 0.05
- V40L (p.Val40Leu), ExAC rs199639961, TOPMed rs199639961, gnomAD rs199639961, MetaLR 0.47, MetaSVM -0.19, Uncertain significance
- V40M (p.Val40Met), rs199639961, ClinGen CA10509247, ClinVar RCV001224587, ClinVar RCV002339601, REVEL 0.37, MetaLR 0.47, Uncertain significance, Inborn genetic diseases; X-linked lymphoproliferative disease due to SH2D1A defi
- V40A (p.Val40Ala), gnomAD X-124346761-T-C, REVEL 0.15, MetaLR 0.29
- V40V (p.Val40Val), rs1488638073, gnomAD X-124346762-G-T, CADD 14.90
- Y41* (p.Tyr41Ter), TOPMed rs1208526451, gnomAD rs1208526451
- Y41F (p.Tyr41Phe), Ensembl rs2147519512
- Y41N (p.Tyr41Asn), rs2522797429, ClinGen CA414122427, ClinVar RCV002295083, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- C42* (p.Cys42Ter), rs2522797441, ClinGen CA414122441, ClinVar RCV003510656, Pathogenic, in XLP1
- C42W (p.Cys42Trp), UniProt VAR 048012, Pathogenic, in XLP1
- C42Y (p.Cys42Tyr), UniProt VAR 088140, MetaLR 0.81, MetaSVM 0.72, Uncertain significance, in XLP1
- L43L (p.Leu43Leu), rs1569527113, gnomAD X-124346771-A-G, CADD 8.98
- C44Y (p.Cys44Tyr), rs2059993925, ClinGen CA414122452, ClinVar RCV001215514, Ensembl rs2059993925, AlphaMissense 0.99, MetaLR 0.83, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- V45V (p.Val45Val), rs1330193938, gnomAD X-124346777-G-C, CADD 7.46
- L46P (p.Leu46Pro), Ensembl rs2147519519
- L46V (p.Leu46Val), Ensembl rs2147519518, MetaLR 0.61, MetaSVM -0.16
- Y47C (p.Tyr47Cys), rs2522814875, ClinGen CA414123382, ClinVar RCV002304850, REVEL 0.47, MetaLR 0.39, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- Y47H (p.Tyr47His), gnomAD X-124365762-T-C, REVEL 0.27, MetaLR 0.36
- Y47F (p.Tyr47Phe), gnomAD X-124365763-A-T, REVEL 0.27, MetaLR 0.34
- H48N (p.His48Asn), gnomAD X-124365765-C-A, REVEL 0.32, MetaLR 0.78
- H48Y (p.His48Tyr), gnomAD X-124365765-C-T, REVEL 0.39, MetaLR 0.87
- H48L (p.His48Leu), gnomAD X-124365766-A-T, REVEL 0.40, MetaLR 0.84
- H48R (p.His48Arg), gnomAD X-124365766-A-G, REVEL 0.29, MetaLR 0.79
- H48Q (p.His48Gln), gnomAD X-124365767-C-A, REVEL 0.31, MetaLR 0.62
- H48P (p.His48Pro), gnomAD X-124365782-A-C, CADD 9.83, SIFT 0.01
- G49S (p.Gly49Ser), cosmic curated COSV10075, ESP rs139045675, ExAC rs139045675, TOPMed rs139045675, REVEL 0.65, MetaLR 0.94, Uncertain significance, Inborn genetic diseases
- G49V (p.Gly49Val), rs2147531318, ClinGen CA414123412, ClinVar RCV001920267, Ensembl rs2147531318, AlphaMissense 0.95, MetaLR 0.97, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- G49D (p.Gly49Asp), gnomAD X-124365769-G-A, REVEL 0.69, MetaLR 0.92
- Y50* (p.Tyr50Ter), rs1556620698, ClinGen CA414123435, ClinVar RCV000624095, Ensembl rs1556620698, CADD 36.00, SIFT 0.12, Pathogenic
- Y50H (p.Tyr50His), gnomAD X-124365771-T-C, REVEL 0.35, MetaLR 0.47
- Y50F (p.Tyr50Phe), gnomAD X-124365772-A-T, REVEL 0.28, MetaLR 0.38
- Y50C (p.Tyr50Cys), gnomAD X-124365772-A-G, REVEL 0.57, MetaLR 0.58
- I51T (p.Ile51Thr), rs2522814895, ClinGen CA414123444, ClinVar RCV003622577, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- I51V (p.Ile51Val), gnomAD X-124365774-A-G, REVEL 0.22, MetaLR 0.15
- Y52I (p.Tyr52Ile), gnomAD X-124365774-AT-A, CADD 32.00
- Y52H (p.Tyr52His), gnomAD X-124365777-T-C, REVEL 0.57, MetaLR 0.73
- Y52C (p.Tyr52Cys), gnomAD X-124365778-A-G, REVEL 0.70, MetaLR 0.77
- Y52F (p.Tyr52Phe), gnomAD X-124365778-A-T, REVEL 0.58, MetaLR 0.76
- T53I (p.Thr53Ile), rs2522814903, ClinGen CA414123480, ClinVar RCV003153153, UniProt VAR 048014, REVEL 0.87, MetaLR 0.83, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- T53M (p.Thr53Met), rs765804146, gnomAD X-124365767-C-T, CADD 6.12, SIFT 0.20
- T53A (p.Thr53Ala), gnomAD X-124365780-A-G, REVEL 0.79, MetaLR 0.81
- T53K (p.Thr53Lys), gnomAD X-124365781-C-A, REVEL 0.77, MetaLR 0.80
- Y54* (p.Tyr54Ter), rs2522814914, ClinVar RCV004560455, CADD 35.00, SIFT 0.03, Likely pathogenic, in XLP1
- Y54C (p.Tyr54Cys), UniProt VAR 048015, Pathogenic, in XLP1
- Y54N (p.Tyr54Asn), rs2147531326, ClinGen CA414123488, ClinVar RCV002250349, Ensembl rs2147531326, AlphaMissense 0.19, Pathogenic, X-linked lymphoproliferative disease due to SH2D1A deficiency
- Y54H (p.Tyr54His), gnomAD X-124365783-T-C, REVEL 0.92, MetaLR 0.85
- R55* (p.Arg55Ter), rs111033623, ClinGen CA255589, cosmic curated COSV63579, ClinVar RCV000011645, CADD 36.00, Pathogenic, in XLP1
- R55L (p.Arg55Leu), rs111033630, ClinGen CA255607, cosmic curated COSV63579, ClinVar RCV000011657, AlphaMissense 0.15, Pathogenic, X-linked lymphoproliferative disease due to SH2D1A deficiency
- R55Q (p.Arg55Gln), rs111033630, ClinGen CA414123516, NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, REVEL 0.87, AlphaMissense 0.15, Conflicting interpretations, not provided; Lymphoproliferative disorder; X-linked lymphoproliferative disease
- R55R (p.Arg55Arg), gnomAD X-124365786-C-A, CADD 12.60
- R55K (p.Arg55Lys), gnomAD X-124365797-G-A, CADD 10.30, SIFT 0.15
- V56A (p.Val56Ala), rs2147531344, ClinGen CA414123538, ClinVar RCV002263564, ClinVar RCV003403759, AlphaMissense 0.21, Uncertain significance, SH2D1A-related disorder; not provided
- V56M (p.Val56Met), gnomAD X-124365789-G-A, REVEL 0.81, MetaLR 0.96
- S57P (p.Ser57Pro), UniProt VAR 048016, REVEL 0.71, MetaLR 0.69, Uncertain significance, in one XLP1 patient
- S57Y (p.Ser57Tyr), gnomAD X-124365793-C-A, REVEL 0.46, MetaLR 0.35
- Q58* (p.Gln58Ter), rs111033628, ClinGen CA255592, ClinVar RCV000011646, Ensembl rs111033628, Pathogenic
- Q58R (p.Gln58Arg), TOPMed rs2060052675, REVEL 0.36, MetaLR 0.45
- Q58K (p.Gln58Lys), gnomAD X-124365795-C-A, REVEL 0.18, MetaLR 0.36
- Q58L (p.Gln58Leu), gnomAD X-124365806-A-T, CADD 9.78, SIFT 0.00
- T59I (p.Thr59Ile), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, MetaLR 0.71, MetaSVM 0.60, Variant assessed as somatic; moderate impact.
- T59K (p.Thr59Lys), gnomAD X-124365799-C-A, REVEL 0.52, MetaLR 0.55
- E60K (p.Glu60Lys), gnomAD X-124365801-G-A, REVEL 0.36, MetaLR 0.83
- T61A (p.Thr61Ala), gnomAD X-124365804-A-G, REVEL 0.38, MetaLR 0.76
- T61K (p.Thr61Lys), gnomAD X-124365805-C-A, REVEL 0.53, MetaLR 0.84
- G62S (p.Gly62Ser), gnomAD X-124365807-G-A, REVEL 0.84, MetaLR 0.96
- G62D (p.Gly62Asp), gnomAD X-124365808-G-A, REVEL 0.77, MetaLR 0.93
- G62* (p.Gly62Ter), gnomAD X-124365814-G-T, REVEL 0.72, MetaLR 0.90
- S63C (p.Ser63Cys), rs1290371898, ClinGen CA414123658, ClinVar RCV004513497, AlphaMissense 0.11, Uncertain significance, Inborn genetic diseases
- S63F (p.Ser63Phe), cosmic curated COSV63579, gnomAD rs1290371898, REVEL 0.64, AlphaMissense 0.11
- S63Y (p.Ser63Tyr), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, REVEL 0.62, MetaLR 0.91, Variant assessed as somatic; moderate impact.
- S63P (p.Ser63Pro), gnomAD X-124365810-T-C, REVEL 0.77, MetaLR 0.95
- S63* (p.Ser63Ter), gnomAD X-124370236-C-A, REVEL 0.52, MetaLR 0.78
- W64* (p.Trp64Ter), rs746035909, ClinGen CA10509271, ClinVar RCV001949632, ExAC rs746035909, CADD 43.00, SIFT 0.11, Pathogenic
- W64C (p.Trp64Cys), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, MetaLR 0.94, MetaSVM 1.09, Variant assessed as somatic; moderate impact.
- W64R (p.Trp64Arg), gnomAD X-124365813-T-C, REVEL 0.86, MetaLR 0.95
- S65G (p.Ser65Gly), gnomAD X-124365816-A-G, REVEL 0.51, MetaLR 0.87
- S65N (p.Ser65Asn), gnomAD X-124365817-G-A, REVEL 0.42, MetaLR 0.90
- S65P (p.Ser65Pro), rs775759946, gnomAD X-124370247-T-C, AlphaMissense 0.23, MetaLR 0.81
- S65F (p.Ser65Phe), rs1012239614, gnomAD X-124370266-C-T, CADD 9.60, SIFT 1.00
- A66P (p.Ala66Pro), rs770028051, ClinGen CA10509272, ClinVar RCV003066640, ExAC rs770028051, REVEL 0.88, MetaLR 0.97, Uncertain significance, X-linked lymphoproliferative disease due to SH2D1A deficiency
- A66T (p.Ala66Thr), gnomAD X-124365819-G-A, REVEL 0.73, MetaLR 0.94
- A66D (p.Ala66Asp), gnomAD X-124365820-C-A, REVEL 0.85, MetaLR 0.96
- A66V (p.Ala66Val), gnomAD X-124365820-C-T, REVEL 0.64, MetaLR 0.86
- E67G (p.Glu67Gly), UniProt VAR 088143, REVEL 0.81, MetaLR 0.87, Uncertain significance, in XLP1
- E67K (p.Glu67Lys), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, REVEL 0.79, MetaLR 0.91, Uncertain significance, in XLP1
- T68I (p.Thr68Ile), rs111033627, ClinGen CA255602, ClinVar RCV000011652, UniProt VAR 005613, AlphaMissense 0.92, MetaLR 0.82, Pathogenic, in XLP1
- T68K (p.Thr68Lys), gnomAD X-124370177-C-A, REVEL 0.68, MetaLR 0.73
- A69T (p.Ala69Thr), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, REVEL 0.36, MetaLR 0.56, Variant assessed as somatic; moderate impact.
- A69A (p.Ala69Ala), rs1056354956, gnomAD X-124370181-A-G, CADD 9.90, SIFT 0.00
- P70L (p.Pro70Leu), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, NCI-TCGA Cosmic COSV6357, Variant assessed as somatic; moderate impact.
- P70S (p.Pro70Ser), NCI-TCGA TCGA novel, MetaLR 0.75, MetaSVM 0.59, Variant assessed as somatic; moderate impact.
- P70T (p.Pro70Thr), gnomAD X-124370182-C-A, REVEL 0.62, MetaLR 0.75
- P70P (p.Pro70Pro), gnomAD X-124370184-T-C, CADD 9.16, SIFT 0.29
- G71A (p.Gly71Ala), gnomAD rs1434069108, REVEL 0.78, MetaLR 0.86
- V72A (p.Val72Ala), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, Variant assessed as somatic; moderate impact.
- V72I (p.Val72Ile), rs1472284481, NCI-TCGA Cosmic COSV6357, cosmic curated COSV63579, gnomAD rs1472284481, AlphaMissense 0.11, MetaLR 0.57, Variant assessed as somatic; moderate impact.
- V72V (p.Val72Val), gnomAD X-124370190-A-G, CADD 7.87, SIFT 0.04
- H73Q (p.His73Gln), rs954824608, ClinGen CA414124395, ClinVar RCV001237812, ClinVar RCV002069308, REVEL 0.26, MetaLR 0.63, Conflicting interpretations, X-linked lymphoproliferative disease due to SH2D1A deficiency; not provided
- H73R (p.His73Arg), TOPMed rs2060065924
- H73Y (p.His73Tyr), NCI-TCGA Cosmic COSV6357, cosmic curated COSV63578, MetaLR 0.87, MetaSVM 0.94, Variant assessed as somatic; moderate impact.
- H73H (p.His73His), rs954824608, gnomAD X-124370193-T-C, CADD 8.69, SIFT 0.51
- K74R (p.Lys74Arg), gnomAD X-124365803-A-G, CADD 10.60, SIFT 0.12
- R75I (p.Arg75Ile), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10075, NCI-TCGA Cosmic COSV6357, REVEL 0.78, MetaLR 0.79, Variant assessed as somatic; moderate impact.
- R75R (p.Arg75Arg), rs371553659, gnomAD X-124370199-A-G, CADD 11.60, SIFT 0.11
Public SH2D1A analysis runs
- SH2D1A analysis run — SH2D1A (299 variants) — completed 2026-08-19