CD40 — 276 ClinVar variants
All ClinVar germline CD40 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 64 flagged for review →
9 Pathogenic · 6 Likely pathogenic · 10 Conflicting · 24 Benign · 5 Benign/Likely benign · 140 Likely benign · 82 Uncertain significance
Full CD40 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 64
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 2
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
CD40 p.Glu144Lys
Likely pathogenic
Single submitter
hyper-IgM syndrome type 3
- CD40 p.Gly149Ser Likely pathogenic Single submitter
Predictors lean, ClinVar uncertain 30
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
CD40 p.Ala25Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CD40 p.Arg123His Uncertain significance Multiple submitters
-
CD40 p.Ile204Val
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CD40 p.Ile208Val
Uncertain significance
Multiple submitters
hyper-IgM syndrome type 3
-
CD40 p.Pro260Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CD40 p.Val138Ala
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CD40 p.Ala115Asp Uncertain significance Single submitter
- CD40 p.Ala115Val Uncertain significance Single submitter
- CD40 p.Ala17Ser Uncertain significance Single submitter
- CD40 p.Ala248Val Uncertain significance Single submitter
- CD40 p.Arg270Ser Uncertain significance Single submitter
- CD40 p.Arg90Gln Uncertain significance Single submitter
- CD40 p.Asn224Asp Uncertain significance Single submitter
-
CD40 p.Asp240Asn
Uncertain significance
Single submitter
Inborn genetic diseases
- CD40 p.Asp241Asn Uncertain significance Single submitter
- CD40 p.Cys8Gly Uncertain significance Single submitter
- CD40 p.Gln36Arg Uncertain significance Single submitter
- CD40 p.Glu232Lys Uncertain significance Single submitter
- CD40 p.Glu98Val Uncertain significance Single submitter
- CD40 p.Gly63Arg Uncertain significance Single submitter
- CD40 p.Gly63Ser Uncertain significance Single submitter
- CD40 p.Leu209Phe Uncertain significance Single submitter
- CD40 p.Leu87Val Uncertain significance Single submitter
- CD40 p.Lys170Glu Uncertain significance Single submitter
-
CD40 p.Lys225Glu
Uncertain significance
Single submitter
Inborn genetic diseases
- CD40 p.Ser126Leu Uncertain significance Single submitter
- CD40 p.Ser49Asn Uncertain significance Single submitter
- CD40 p.Val138Ile Uncertain significance Single submitter
- CD40 p.Val185Ile Uncertain significance Single submitter
- CD40 p.Val261Ala Uncertain significance Single submitter
Predictors split 32
The independent predictors disagree with each other — read with care.
-
CD40 p.Asn180Lys
Uncertain significance
Multiple submitters
CD40-related disorder
-
CD40 p.Ser124Leu
Benign
Multiple submitters
hyper-IgM syndrome type 3
-
CD40 p.Ser245Cys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CD40 p.Ser245Phe
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CD40 p.Thr112Lys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CD40 p.Thr112Met
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CD40 p.Ala157Thr Uncertain significance Single submitter
- CD40 p.Arg123Cys Uncertain significance Single submitter
- CD40 p.Arg191Trp Uncertain significance Single submitter
- CD40 p.Arg90Trp Uncertain significance Single submitter
- CD40 p.Asn34Ser Uncertain significance Single submitter
-
CD40 p.Asp241Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
- CD40 p.Gln30Arg Uncertain significance Single submitter
-
CD40 p.Glu144Gln
Uncertain significance
Single submitter
Inborn genetic diseases
- CD40 p.Glu159Lys Uncertain significance Single submitter
- CD40 p.Glu268Asp Uncertain significance Single submitter
- CD40 p.Gly128Ser Uncertain significance Single submitter
- CD40 p.Gly63Asp Uncertain significance Single submitter
- CD40 p.His110Arg Uncertain significance Single submitter
- CD40 p.Lys217Asn Uncertain significance Single submitter
-
CD40 p.Phe129Cys
Uncertain significance
Single submitter
Inborn genetic diseases
-
CD40 p.Pro127Ser
Uncertain significance
Single submitter
hyper-IgM syndrome type 3
- CD40 p.Pro85Leu Uncertain significance Single submitter
-
CD40 p.Ser39Phe
Uncertain significance
Single submitter
Inborn genetic diseases
-
CD40 p.Thr104Ile
Uncertain significance
Single submitter
hyper-IgM syndrome type 3
- CD40 p.Thr136Ala Uncertain significance Single submitter
- CD40 p.Thr55Ile Uncertain significance Single submitter
-
CD40 p.Thr57Met
Conflicting
Single submitter
hyper-IgM syndrome type 3
- CD40 p.Thr70Ala Uncertain significance Single submitter
-
CD40 p.Thr70Asn
Uncertain significance
Single submitter
Inborn genetic diseases
-
CD40 p.Val91Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
CD40 p.Val91Ile
Uncertain significance
Single submitter
Inborn genetic diseases
All CD40 variants
Pathogenic 9
- p.Gln133Ter Single submitter
- p.Glu53Ter Single submitter
- p.Lys29fs Single submitter
- p.Thr96fs Single submitter
- p.Trp11Ter Single submitter
- c.257-2A>T No assertion criteria hyper-IgM syndrome type 3
- p.Cys83Arg No assertion criteria hyper-IgM syndrome type 3
- p.Ile33del No assertion criteria hyper-IgM syndrome type 3
- p.Thr136= No assertion criteria hyper-IgM syndrome type 3
Likely pathogenic 6
- c.497+1G>A Single submitter
- c.646+1G>A Single submitter
- p.Glu144Lys Single submitter hyper-IgM syndrome type 3 ⚠
- p.Gly149Ser Single submitter ⚠
- p.Met1fs Single submitter
- p.Ter278AlaextTer? Single submitter
Conflicting classifications of pathogenicity 10
- c.256+2T>C Single submitter hyper-IgM syndrome type 3
- c.256+8C>T Single submitter hyper-IgM syndrome type 3
- c.498-7T>C Single submitter hyper-IgM syndrome type 3
- p.Cys83= Single submitter hyper-IgM syndrome type 3
- p.Pro127= Single submitter hyper-IgM syndrome type 3
- p.Pro250= Single submitter hyper-IgM syndrome type 3
- p.Ser113= Single submitter hyper-IgM syndrome type 3
- p.Thr57Met Single submitter hyper-IgM syndrome type 3 ⚠
- p.Val148= Single submitter hyper-IgM syndrome type 3
- p.Val18= Single submitter
Benign 24
- c.131-22C>G Multiple submitters
- c.498-168G>T Multiple submitters
- c.51+53G>A Multiple submitters
- c.51+71C>T Multiple submitters
- c.559+36G>C Multiple submitters hyper-IgM syndrome type 3
- c.646+28G>A Multiple submitters
- c.646+45A>C Multiple submitters
- c.647-3dup Multiple submitters hyper-IgM syndrome type 3
- c.675+216A>G Multiple submitters
- c.676-114G>A Multiple submitters
- c.-1T>C Multiple submitters hyper-IgM syndrome type 3
- c.-41C>T Multiple submitters hyper-IgM syndrome type 3
- c.*135C>G Multiple submitters hyper-IgM syndrome type 3
- c.*316G>C Multiple submitters hyper-IgM syndrome type 3
- p.Phe202= Multiple submitters hyper-IgM syndrome type 3
- p.Ser124Leu Multiple submitters hyper-IgM syndrome type 3 ⚠
- c.256+109G>A Single submitter
- c.646+27G>T Single submitter hyper-IgM syndrome type 3
- c.647-3del Single submitter
- c.647-4_647-3del Single submitter
- c.647-4_647-3dup Single submitter
- c.675+12del Single submitter
- c.-69delT Single submitter
- p.Ser49= Single submitter
Benign/Likely benign 5
- c.403+20A>G Multiple submitters hyper-IgM syndrome type 3
- c.52-15C>T Multiple submitters hyper-IgM syndrome type 3
- p.Ala207= Multiple submitters hyper-IgM syndrome type 3
- p.Pro227= Multiple submitters
- p.Pro239= Multiple submitters hyper-IgM syndrome type 3
Likely benign 140
- c.498-14G>A Multiple submitters
- p.Gln234= Multiple submitters
- p.Phe158= Multiple submitters
- c.130+14C>T Single submitter
- c.131-10T>C Single submitter
- c.131-11A>C Single submitter
- c.131-11A>G Single submitter
- c.256+14T>C Single submitter
- c.256+16G>A Single submitter
- c.256+20A>G Single submitter
- c.256+7G>A Single submitter
- c.257-13C>T Single submitter
- c.257-16G>A Single submitter
- c.257-17_257-14del Single submitter
- c.257-19C>T Single submitter
- c.257-8C>T Single submitter
- c.403+11C>A Single submitter
- c.403+11C>G Single submitter
- c.403+11C>T Single submitter
- c.403+18G>T Single submitter
- c.404-10C>T Single submitter
- c.404-120A>T Single submitter
- c.404-12A>C Single submitter
- c.404-13C>A Single submitter
- c.404-20C>G Single submitter
- c.404-4C>G Single submitter
- c.497+14T>C Single submitter
- c.498-15C>T Single submitter
- c.498-17C>T Single submitter
- c.498-30_498-11del Single submitter
- c.51+15C>T Single submitter
- c.51+16C>T Single submitter
- c.51+17C>T Single submitter
- c.51+19G>A Single submitter
- c.52-10C>A Single submitter
- c.52-19T>C Single submitter
- c.559+12A>G Single submitter
- c.559+13C>A Single submitter
- c.559+15A>G Single submitter
- c.559+18G>A Single submitter
- c.560-10A>T Single submitter
- c.560-11_560-10insT Single submitter
- c.560-119C>A Single submitter
- c.560-20T>G Single submitter
- c.560-4C>T Single submitter
- c.560-6C>G Single submitter
- c.646+14dup Single submitter
- c.646+17_646+18del Single submitter
- c.646+17G>C Single submitter
- c.646+20G>A Single submitter
- c.646+7C>T Single submitter
- c.646+8C>T Single submitter
- c.647-14_647-3del Single submitter
- c.647-16_647-3del Single submitter
- c.647-18T>A Single submitter
- c.647-20_647-19insC Single submitter
- c.675+13T>C Single submitter
- c.675+14G>C Single submitter
- c.675+18A>G Single submitter
- c.675+19C>A Single submitter
- c.675+19C>G Single submitter
- c.675+19C>T Single submitter
- c.675+20C>G Single submitter
- c.675+9C>A Single submitter
- c.675+9C>T Single submitter
- c.676-13C>T Single submitter
- c.676-14C>T Single submitter
- c.676-18C>T Single submitter
- c.676-46C>T Single submitter
- c.676-4C>T Single submitter
- p.Ala177= Single submitter
- p.Ala25= Single submitter
- p.Arg191= Single submitter
- p.Arg270= Single submitter
- p.Arg3= Single submitter
- p.Asn153= Single submitter
- p.Asp240= Single submitter
- p.Asp241= Single submitter
- p.Asp84= Single submitter
- p.Cys105= Single submitter
- p.Cys111= Single submitter
- p.Cys125= Single submitter
- p.Cys143= Single submitter
- p.Cys146= Single submitter
- p.Cys258= Single submitter
- p.Cys26= Single submitter
- p.Cys41= Single submitter
- p.Cys62= Single submitter
- p.Cys8= Single submitter
- p.Gln175= Single submitter
- p.Gln259= Single submitter
- p.Gln30= Single submitter
- p.Gln36= Single submitter
- p.Gln79= Single submitter
- p.Glu56= Single submitter
- p.Gly128= Single submitter
- p.Gly257= Single submitter
- p.Gly44= Single submitter
- p.His110= Single submitter
- p.His122= Single submitter
- p.His19= Single submitter
- p.His256= Single submitter
- p.His80= Single submitter
- p.Ile198= Single submitter
- p.Leu15= Single submitter
- p.Leu209= Single submitter
- p.Leu210= Single submitter
- p.Leu32= Single submitter
- p.Leu4= Single submitter
- p.Leu40= Single submitter
- p.Leu68= Single submitter
- p.Leu87= Single submitter
- p.Lys132= Single submitter
- p.Lys220= Single submitter Inborn genetic diseases
- p.Phe67= Single submitter
- p.Pro145= Single submitter
- p.Pro147= Single submitter
- p.Pro163= Single submitter
- p.Pro227Ala Single submitter
- p.Pro229= Single submitter
- p.Pro23= Single submitter
- p.Pro260= Single submitter
- p.Ser124= Single submitter
- p.Ser126= Single submitter
- p.Ser155= Single submitter
- p.Ser156= Single submitter
- p.Ser65= Single submitter
- p.Ser97= Single submitter
- p.Thr112= Single submitter
- p.Thr16= Single submitter
- p.Thr182= Single submitter
- p.Thr262= Single submitter
- p.Thr52= Single submitter
- p.Thr55= Single submitter
- p.Thr57= Single submitter
- p.Thr96= Single submitter
- p.Val273= Single submitter
- p.Val9= Single submitter
- p.Val91= Single submitter
- p.His19Gln No assertion criteria
Uncertain significance 82
- c.256+5G>A Multiple submitters
- c.*178G>A Multiple submitters hyper-IgM syndrome type 3
- c.*547A>T Multiple submitters hyper-IgM syndrome type 3
- p.Ala25Ser Multiple submitters Inborn genetic diseases ⚠
- p.Arg123His Multiple submitters ⚠
- p.Asn180Lys Multiple submitters CD40-related disorder ⚠
- p.Ile204Val Multiple submitters Inborn genetic diseases ⚠
- p.Ile208Val Multiple submitters hyper-IgM syndrome type 3 ⚠
- p.Pro260Ser Multiple submitters Inborn genetic diseases ⚠
- p.Ser245Cys Multiple submitters Inborn genetic diseases ⚠
- p.Ser245Phe Multiple submitters Inborn genetic diseases ⚠
- p.Thr112Lys Multiple submitters Inborn genetic diseases ⚠
- p.Thr112Met Multiple submitters Inborn genetic diseases ⚠
- p.Val138Ala Multiple submitters Inborn genetic diseases ⚠
- c.256+17G>T Single submitter
- c.256+4C>T Single submitter
- c.257-7_257-3del Single submitter
- c.403+6T>A Single submitter
- c.498-35TG[4] Single submitter
- c.498-4A>T Single submitter
- c.51+7T>C Single submitter
- c.52-13A>G Single submitter
- c.560-3C>T Single submitter
- c.-55C>G Single submitter hyper-IgM syndrome type 3
- c.-61G>T Single submitter hyper-IgM syndrome type 3
- c.-67G>T Single submitter hyper-IgM syndrome type 3
- c.*310C>G Single submitter hyper-IgM syndrome type 3
- c.*372A>C Single submitter hyper-IgM syndrome type 3
- c.*560C>T Single submitter hyper-IgM syndrome type 3
- c.*676C>T Single submitter hyper-IgM syndrome type 3
- c.*677G>A Single submitter hyper-IgM syndrome type 3
- c.*85G>T Single submitter hyper-IgM syndrome type 3
- p.Ala115Asp Single submitter ⚠
- p.Ala115Val Single submitter ⚠
- p.Ala157Thr Single submitter ⚠
- p.Ala17Ser Single submitter ⚠
- p.Ala248Val Single submitter ⚠
- p.Arg123Cys Single submitter ⚠
- p.Arg191Trp Single submitter ⚠
- p.Arg270Ser Single submitter ⚠
- p.Arg90Gln Single submitter ⚠
- p.Arg90Trp Single submitter ⚠
- p.Asn224Asp Single submitter ⚠
- p.Asn34Ser Single submitter ⚠
- p.Asp240Asn Single submitter Inborn genetic diseases ⚠
- p.Asp241Asn Single submitter ⚠
- p.Asp241Tyr Single submitter Inborn genetic diseases ⚠
- p.Cys8Gly Single submitter ⚠
- p.Gln30Arg Single submitter ⚠
- p.Gln36Arg Single submitter ⚠
- p.Glu144Gln Single submitter Inborn genetic diseases ⚠
- p.Glu159Lys Single submitter ⚠
- p.Glu232Lys Single submitter ⚠
- p.Glu268Asp Single submitter ⚠
- p.Glu98Val Single submitter ⚠
- p.Gly128Ser Single submitter ⚠
- p.Gly63Arg Single submitter ⚠
- p.Gly63Asp Single submitter ⚠
- p.Gly63Ser Single submitter ⚠
- p.His110Arg Single submitter ⚠
- p.Leu209Phe Single submitter ⚠
- p.Leu87Val Single submitter ⚠
- p.Lys170Glu Single submitter ⚠
- p.Lys217Asn Single submitter ⚠
- p.Lys225Glu Single submitter Inborn genetic diseases ⚠
- p.Phe129Cys Single submitter Inborn genetic diseases ⚠
- p.Pro127Ser Single submitter hyper-IgM syndrome type 3 ⚠
- p.Pro43= Single submitter
- p.Pro85Leu Single submitter ⚠
- p.Ser126Leu Single submitter ⚠
- p.Ser39Phe Single submitter Inborn genetic diseases ⚠
- p.Ser49Asn Single submitter ⚠
- p.Thr104Ile Single submitter hyper-IgM syndrome type 3 ⚠
- p.Thr136Ala Single submitter ⚠
- p.Thr55Ile Single submitter ⚠
- p.Thr70Ala Single submitter ⚠
- p.Thr70Asn Single submitter Inborn genetic diseases ⚠
- p.Val138Ile Single submitter ⚠
- p.Val185Ile Single submitter ⚠
- p.Val261Ala Single submitter ⚠
- p.Val91Ala Single submitter Inborn genetic diseases ⚠
- p.Val91Ile Single submitter Inborn genetic diseases ⚠