SH2D1A — 162 ClinVar variants
All ClinVar germline SH2D1A variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 44 flagged for review →
28 Pathogenic · 1 Pathogenic/Likely pathogenic · 12 Likely pathogenic · 13 Conflicting · 17 Benign · 6 Benign/Likely benign · 29 Likely benign · 56 Uncertain significance
Full SH2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 44
Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.
Predictors vs ClinVar 1
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
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SH2D1A p.Asp2Gly
Likely pathogenic
Multiple submitters
SH2D1A-related disorder
Predictors agree, ClinVar conflicts 7
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
SH2D1A p.Ala3Ser
Conflicting
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Arg55Gln
Conflicting
Single submitter
lymphoproliferative syndrome
-
SH2D1A p.His73Gln
Conflicting
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.His8Pro
Conflicting
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Lys18Arg
Conflicting
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
- SH2D1A p.Pro97Leu Conflicting Single submitter
-
SH2D1A p.Ser34Arg
Conflicting
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
Predictors lean, ClinVar uncertain 27
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
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SH2D1A p.Cys124Ser
Uncertain significance
Multiple submitters
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Ser63Pro
Uncertain significance
Multiple submitters
X-linked lymphoproliferative disease due to SH2D1A deficiency
- SH2D1A p.Ala86Pro Uncertain significance Single submitter
-
SH2D1A p.Ala86Thr
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Arg32Lys
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Arg78Trp
Uncertain significance
Single submitter
Inborn genetic diseases
- SH2D1A p.Asp26Tyr Uncertain significance Single submitter
- SH2D1A p.Asp33Gly Uncertain significance Single submitter
-
SH2D1A p.Asp91Glu
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Cys44Tyr
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Gln58Glu
Uncertain significance
Single submitter
Inborn genetic diseases
-
SH2D1A p.Gly113Val
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Gly39Val
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Gly49Val
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.His8Arg
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Ile117Met
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Ile11Asn
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Ile96Thr
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Leu31Pro
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Leu98Pro
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Pro121Leu
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Pro38Ser
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Ser63Cys
Uncertain significance
Single submitter
Inborn genetic diseases
-
SH2D1A p.Tyr41Asn
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Tyr47Cys
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Val37Met
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Val45Gly
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
Predictors split 9
The independent predictors disagree with each other — read with care.
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SH2D1A p.Val102Ile
Uncertain significance
Multiple submitters
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Val56Ala
Uncertain significance
Multiple submitters
SH2D1A-related disorder
-
SH2D1A p.Ala66Pro
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Glu14Gly
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Gly49Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
SH2D1A p.Ile51Thr
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
-
SH2D1A p.Thr53Ile
Conflicting
Single submitter
SH2D1A-related disorder
-
SH2D1A p.Thr68Arg
Likely pathogenic
Single submitter
Lymphoproliferative syndrome with absent SAP expression
-
SH2D1A p.Thr68Ile
Uncertain significance
Single submitter
X-linked lymphoproliferative disease due to SH2D1A deficiency
All SH2D1A variants
Pathogenic 28
- c.138-1G>A Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Arg55Ter Multiple submitters X-linked lymphoproliferative syndrome
- p.Asn82fs Multiple submitters SH2D1A-related disorder
- p.Trp64Ter Multiple submitters X-linked lymphoproliferative syndrome
- c.138-2A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+1dup Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+1G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+1G>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+2T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.202-1G>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Cys42Ter Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Gln58Ter Single submitter Lymphoproliferative syndrome with absent SAP expression
- p.Gln99Ter Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ile84Thr Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Met1Val Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ser36fs Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Tyr50Ter Single submitter Inborn genetic diseases
- p.Tyr54Asn Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Tyr7Cys Single submitter X-linked lymphoproliferative syndrome
- c.137+5G>C No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.138-1G>T No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.149_201+106del No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.-10C>T No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Arg32Thr No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Arg55Leu No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Met1Ile No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Pro101Leu No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ter129Arg No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
Pathogenic/Likely pathogenic 1
- p.Met1Thr Multiple submitters SH2D1A-related disorder
Likely pathogenic 12
- c.201+3A>G Multiple submitters autoinflammatory syndrome
- p.Asp2Gly Multiple submitters SH2D1A-related disorder ⚠
- c.137+1G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.197_201+9del Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.199_201+23del Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+1_201+4del Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.202-8T>G Single submitter
- p.Gln88fs Single submitter autoinflammatory syndrome
- p.Leu21_Ala22insLeu Single submitter Lymphoproliferative syndrome with absent SAP expression
- p.Thr68Arg Single submitter Lymphoproliferative syndrome with absent SAP expression ⚠
- p.Tyr54Ter Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.138-3C>G No assertion criteria X-linked lymphoproliferative disease due to SH2D1A deficiency
Conflicting classifications of pathogenicity 13
- c.202-5del Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.-124T>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*862T>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ala3Ser Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Arg55Gln Single submitter lymphoproliferative syndrome ⚠
- p.Arg75= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Asp91= Single submitter autoinflammatory syndrome
- p.His73Gln Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.His8Pro Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Lys18Arg Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Pro97Leu Single submitter ⚠
- p.Ser34Arg Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Thr53Ile Single submitter SH2D1A-related disorder ⚠
Benign 17
- c.202-83C>A Multiple submitters
- c.346+114A>G Multiple submitters
- c.*1321A>G Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*212G>A Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*863T>A Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.137+276_137+277del Single submitter
- c.201+20del Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+277_201+278insAAAG Single submitter
- c.201+317T>G Single submitter
- c.-247G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1100C>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1689C>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*203del Single submitter
- c.*257A>T Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*866A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.His48= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ser28= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
Benign/Likely benign 6
- c.138-19G>A Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.346+3A>G Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.347-32_347-28del Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.-318G>C Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.-74T>A Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Gly16= Multiple submitters Inborn genetic diseases
Likely benign 29
- p.Leu125= Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ser110= Multiple submitters Inborn genetic diseases
- c.137+14G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.137+157T>C Single submitter
- c.137+190G>A Single submitter
- c.138-7T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.201+12T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.202-10T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.202-17G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.346+10_346+20del Single submitter
- c.346+6A>T Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.347-12A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Arg13= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Arg32= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Asp122= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.His73= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Leu19= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Leu43= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Leu98= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Lys104= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ser34= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Thr15= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Thr61= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Tyr29= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Tyr41= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Tyr52= Single submitter
- p.Tyr76= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Val40= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.138-12A>G No assertion criteria SH2D1A-related disorder
Uncertain significance 56
- p.Cys124Ser Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ser63Pro Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Val102Ile Multiple submitters X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Val40Met Multiple submitters Inborn genetic diseases
- p.Val56Ala Multiple submitters SH2D1A-related disorder ⚠
- c.137+3_137+6del Single submitter
- c.201+4T>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.202-9_202-7del Single submitter
- c.*1077G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*110T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1192A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1601T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1753A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*1755G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*26A>T Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*511A>G Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*647G>A Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*759G>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- c.*860T>C Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ala66Pro Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ala66Val Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ala86Pro Single submitter ⚠
- p.Ala86Thr Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Arg118_Glu119delinsLys Single submitter
- p.Arg32Lys Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Arg78Trp Single submitter Inborn genetic diseases ⚠
- p.Asp26Tyr Single submitter ⚠
- p.Asp33Gly Single submitter ⚠
- p.Asp91Glu Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Cys44Tyr Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Gln58Glu Single submitter Inborn genetic diseases ⚠
- p.Glu14Gly Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Gly113Val Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Gly39Val Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Gly49Ser Single submitter Inborn genetic diseases ⚠
- p.Gly49Val Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.His8Arg Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ile117Met Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ile11Asn Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ile51Thr Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ile96Thr Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Leu21Arg Single submitter
- p.Leu31Pro Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Leu46= Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Leu98Pro Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Pro121Leu Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Pro38Ser Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Ser28_Ser34dup Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Ser63Cys Single submitter Inborn genetic diseases ⚠
- p.Ter129Gly Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Thr68Ile Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Tyr41Asn Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Tyr47Cys Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Tyr50His Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency
- p.Val37Met Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠
- p.Val45Gly Single submitter X-linked lymphoproliferative disease due to SH2D1A deficiency ⚠