MC2R — 193 ClinVar variants
All ClinVar germline MC2R variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 55 flagged for review →
16 Pathogenic · 4 Pathogenic/Likely pathogenic · 17 Likely pathogenic · 6 Conflicting · 25 Benign · 1 Benign/Likely benign · 18 Likely benign · 106 Uncertain significance
Full MC2R gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 55
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 5
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
MC2R p.Arg137Trp
Pathogenic/Likely pathogenic
Multiple submitters
glucocorticoid deficiency 1
-
MC2R p.Arg146His
Pathogenic/Likely pathogenic
Multiple submitters
Inborn genetic diseases
-
MC2R p.Thr179Met
Likely pathogenic
Single submitter
MC2R-related disorders
-
MC2R p.Val142Leu
Pathogenic
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Ala126Ser
Pathogenic
No assertion criteria
glucocorticoid deficiency 1
Predictors agree, ClinVar conflicts 1
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
MC2R p.Arg145Cys
Conflicting
Single submitter
glucocorticoid deficiency 1
Predictors lean, ClinVar uncertain 34
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
MC2R p.Ala126Val
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
MC2R p.Ala57Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
MC2R p.Arg137Gln
Uncertain significance
Multiple submitters
glucocorticoid deficiency 1
-
MC2R p.Leu190Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
MC2R p.Val25Ile
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
MC2R p.Val45Ile
Uncertain significance
Multiple submitters
glucocorticoid deficiency 1
-
MC2R p.Ala135Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ala135Thr
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Arg145Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Arg201Gln
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Arg279Trp
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Asp20His
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Gly162Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Gly262Ser
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Gly90Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.His139Gln
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile106Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile118Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile154Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile219Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile82Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile85Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Lys206Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Met215Lys
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Met255Ile
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Met89Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ser117Pro
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Ser169Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ser180Leu
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Thr156Met
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Thr159Met
Uncertain significance
Single submitter
Inborn genetic diseases
- MC2R p.Tyr276Asp Uncertain significance Single submitter
-
MC2R p.Val123Met
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Val270Ile
Uncertain significance
Single submitter
glucocorticoid deficiency 1
Predictors split 15
The independent predictors disagree with each other — read with care.
-
MC2R p.Asp104Tyr
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Gly160Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Gly73Asp
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Ile36Asn
Uncertain significance
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Met266Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Met59Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Pro27Arg
Conflicting
Single submitter
glucocorticoid deficiency 1
-
MC2R p.Thr159Arg
Likely pathogenic
Single submitter
MC2R-related disorders
-
MC2R p.Thr222Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
MC2R p.Val175Glu
Uncertain significance
Single submitter
glucocorticoid deficiency 1
- MC2R p.Val49Met Likely pathogenic Single submitter
-
MC2R p.Arg137Pro
Pathogenic
No assertion criteria
Glucocorticoid Deficiency
-
MC2R p.Asp107Asn
Pathogenic
No assertion criteria
glucocorticoid deficiency 1
-
MC2R p.Cys251Phe
Pathogenic
No assertion criteria
glucocorticoid deficiency 1
-
MC2R p.Tyr254Cys
Pathogenic
No assertion criteria
glucocorticoid deficiency 1
All MC2R variants
Pathogenic 16
- p.Ile154fs Multiple submitters glucocorticoid deficiency 1
- p.Ser74Ile Multiple submitters MC2R-related disorders
- p.Leu225Arg Single submitter glucocorticoid deficiency 1
- p.Phe235fs Single submitter glucocorticoid deficiency 1
- p.Tyr193_Val194delinsTer Single submitter
- p.Val142Leu Single submitter glucocorticoid deficiency 1 ⚠
- p.Val187fs Single submitter glucocorticoid deficiency 1
- p.Ala126Ser No assertion criteria glucocorticoid deficiency 1 ⚠
- p.Ala218fs No assertion criteria glucocorticoid deficiency 1
- p.Arg128Cys No assertion criteria glucocorticoid deficiency 1
- p.Arg137Pro No assertion criteria Glucocorticoid Deficiency ⚠
- p.Asp107Asn No assertion criteria glucocorticoid deficiency 1 ⚠
- p.Cys191Ter No assertion criteria Glucocorticoid Deficiency
- p.Cys251Phe No assertion criteria glucocorticoid deficiency 1 ⚠
- p.Ser120Arg No assertion criteria glucocorticoid deficiency 1
- p.Tyr254Cys No assertion criteria glucocorticoid deficiency 1 ⚠
Pathogenic/Likely pathogenic 4
- p.Arg137Trp Multiple submitters glucocorticoid deficiency 1 ⚠
- p.Arg146His Multiple submitters Inborn genetic diseases ⚠
- p.Phe230fs Multiple submitters glucocorticoid deficiency 1
- p.Ser256Phe Multiple submitters MC2R-related disorders
Likely pathogenic 17
- p.Arg128His Single submitter
- p.Arg145fs Single submitter glucocorticoid deficiency 1
- p.Arg201Ter Single submitter glucocorticoid deficiency 1
- p.Arg212fs Single submitter
- p.Asp103Asn Single submitter
- p.Cys245Ter Single submitter glucocorticoid deficiency 1
- p.Cys64fs Single submitter MC2R-related disorders
- p.Gly226Arg Single submitter glucocorticoid deficiency 1
- p.Leu184fs Single submitter glucocorticoid deficiency 1
- p.Leu198Pro Single submitter MC2R-related disorders
- p.Phe119fs Single submitter
- p.Pro273Ser Single submitter
- p.Thr159Arg Single submitter MC2R-related disorders ⚠
- p.Thr179Met Single submitter MC2R-related disorders ⚠
- p.Trp232Ter Single submitter glucocorticoid deficiency 1
- p.Val49Met Single submitter ⚠
- p.Trp155Cys No assertion criteria Glucocorticoid Deficiency
Conflicting classifications of pathogenicity 6
- p.Arg145= Single submitter glucocorticoid deficiency 1
- p.Arg145Cys Single submitter glucocorticoid deficiency 1 ⚠
- p.Ile265= Single submitter glucocorticoid deficiency 1
- p.Pro27Arg Single submitter glucocorticoid deficiency 1 ⚠
- p.Thr143= Single submitter glucocorticoid deficiency 1
- p.Thr179= Single submitter glucocorticoid deficiency 1
Benign 25
- c.-44G>C Multiple submitters glucocorticoid deficiency 1
- c.*1099A>T Multiple submitters glucocorticoid deficiency 1
- c.*111G>A Multiple submitters glucocorticoid deficiency 1
- c.*1604G>C Multiple submitters glucocorticoid deficiency 1
- c.*1885T>C Multiple submitters glucocorticoid deficiency 1
- c.*1896C>T Multiple submitters glucocorticoid deficiency 1
- c.*2138G>T Multiple submitters glucocorticoid deficiency 1
- c.*2394C>G Multiple submitters glucocorticoid deficiency 1
- c.*58G>A Multiple submitters glucocorticoid deficiency 1
- c.*615C>T Multiple submitters glucocorticoid deficiency 1
- c.*685G>A Multiple submitters glucocorticoid deficiency 1
- c.*880C>T Multiple submitters glucocorticoid deficiency 1
- p.Phe278Cys Multiple submitters glucocorticoid deficiency 1
- c.-90T>C Single submitter glucocorticoid deficiency 1
- c.-94G>A Single submitter glucocorticoid deficiency 1
- c.*1061C>A Single submitter glucocorticoid deficiency 1
- c.*1144G>A Single submitter glucocorticoid deficiency 1
- c.*1330A>G Single submitter glucocorticoid deficiency 1
- c.*1759C>A Single submitter glucocorticoid deficiency 1
- c.*1877A>G Single submitter glucocorticoid deficiency 1
- c.*1920T>A Single submitter glucocorticoid deficiency 1
- c.*2426T>C Single submitter glucocorticoid deficiency 1
- c.*2528T>G Single submitter glucocorticoid deficiency 1
- c.*491A>G Single submitter glucocorticoid deficiency 1
- c.*535G>C Single submitter glucocorticoid deficiency 1
Benign/Likely benign 1
- p.Ile106= Multiple submitters
Likely benign 18
- c.*2432A>C Multiple submitters glucocorticoid deficiency 1
- p.Ala252Thr Multiple submitters glucocorticoid deficiency 1
- p.Asn261= Multiple submitters
- p.Thr33Ile Multiple submitters glucocorticoid deficiency 1
- c.-129+87C>T Single submitter
- c.-129+92T>C Single submitter
- c.*117A>T Single submitter glucocorticoid deficiency 1
- c.*1619G>A Single submitter glucocorticoid deficiency 1
- c.*2065G>A Single submitter glucocorticoid deficiency 1
- c.*2224A>C Single submitter glucocorticoid deficiency 1
- c.*2323C>T Single submitter glucocorticoid deficiency 1
- c.*427G>A Single submitter glucocorticoid deficiency 1
- p.Asn13Asp Single submitter Inborn genetic diseases
- p.Asn214= Single submitter
- p.Cys251= Single submitter
- p.Ser7Leu Single submitter Inborn genetic diseases
- p.Ala277= No assertion criteria MC2R-related disorder
- p.Trp297Arg No assertion criteria
Uncertain significance 106
- c.*578C>A Multiple submitters glucocorticoid deficiency 1
- c.*971G>C Multiple submitters glucocorticoid deficiency 1
- c.*996A>T Multiple submitters glucocorticoid deficiency 1
- c.*998T>A Multiple submitters glucocorticoid deficiency 1
- p.Ala126Val Multiple submitters Inborn genetic diseases ⚠
- p.Ala57Glu Multiple submitters Inborn genetic diseases ⚠
- p.Arg137Gln Multiple submitters glucocorticoid deficiency 1 ⚠
- p.Leu190Arg Multiple submitters Inborn genetic diseases ⚠
- p.Val25Ile Multiple submitters Inborn genetic diseases ⚠
- p.Val45Ile Multiple submitters glucocorticoid deficiency 1 ⚠
- c.-117A>T Single submitter glucocorticoid deficiency 1
- c.-129+10T>C Single submitter glucocorticoid deficiency 1
- c.-48T>C Single submitter glucocorticoid deficiency 1
- c.*1000T>A Single submitter glucocorticoid deficiency 1
- c.*1002T>A Single submitter glucocorticoid deficiency 1
- c.*1004T>A Single submitter glucocorticoid deficiency 1
- c.*1010T>A Single submitter glucocorticoid deficiency 1
- c.*1012T>A Single submitter glucocorticoid deficiency 1
- c.*1035G>A Single submitter glucocorticoid deficiency 1
- c.*1039G>A Single submitter glucocorticoid deficiency 1
- c.*1043G>A Single submitter glucocorticoid deficiency 1
- c.*1068A>G Single submitter glucocorticoid deficiency 1
- c.*1092G>A Single submitter glucocorticoid deficiency 1
- c.*1265A>C Single submitter glucocorticoid deficiency 1
- c.*1274T>A Single submitter glucocorticoid deficiency 1
- c.*1452A>G Single submitter glucocorticoid deficiency 1
- c.*1469A>G Single submitter glucocorticoid deficiency 1
- c.*1537A>G Single submitter glucocorticoid deficiency 1
- c.*1667G>A Single submitter glucocorticoid deficiency 1
- c.*1856T>C Single submitter glucocorticoid deficiency 1
- c.*1870A>G Single submitter glucocorticoid deficiency 1
- c.*1917C>A Single submitter glucocorticoid deficiency 1
- c.*1973dup Single submitter
- c.*216G>A Single submitter glucocorticoid deficiency 1
- c.*223T>C Single submitter glucocorticoid deficiency 1
- c.*2409A>G Single submitter glucocorticoid deficiency 1
- c.*2427T>C Single submitter glucocorticoid deficiency 1
- c.*2572G>A Single submitter glucocorticoid deficiency 1
- c.*27C>T Single submitter glucocorticoid deficiency 1
- c.*366G>T Single submitter glucocorticoid deficiency 1
- c.*376G>C Single submitter glucocorticoid deficiency 1
- c.*390A>G Single submitter glucocorticoid deficiency 1
- c.*406C>A Single submitter glucocorticoid deficiency 1
- c.*434T>C Single submitter glucocorticoid deficiency 1
- c.*470G>A Single submitter glucocorticoid deficiency 1
- c.*471C>A Single submitter glucocorticoid deficiency 1
- c.*582C>A Single submitter glucocorticoid deficiency 1
- c.*608A>G Single submitter glucocorticoid deficiency 1
- c.*673C>T Single submitter glucocorticoid deficiency 1
- c.*791A>G Single submitter glucocorticoid deficiency 1
- c.*848A>T Single submitter glucocorticoid deficiency 1
- c.*862T>C Single submitter glucocorticoid deficiency 1
- c.*911A>C Single submitter glucocorticoid deficiency 1
- c.*957C>G Single submitter glucocorticoid deficiency 1
- c.*968AG[14] Single submitter
- c.*990A>T Single submitter glucocorticoid deficiency 1
- c.*992A>T Single submitter glucocorticoid deficiency 1
- c.*994_*1003del Single submitter
- c.*994_*999del Single submitter
- c.*994A>T Single submitter glucocorticoid deficiency 1
- c.*996_*999del Single submitter
- c.*997GT[23] Single submitter
- c.*997GT[24] Single submitter
- c.*997GT[25] Single submitter
- c.*997GT[27] Single submitter
- p.Ala135Ser Single submitter Inborn genetic diseases ⚠
- p.Ala135Thr Single submitter glucocorticoid deficiency 1 ⚠
- p.Arg137= Single submitter glucocorticoid deficiency 1
- p.Arg145Gly Single submitter Inborn genetic diseases ⚠
- p.Arg201Gln Single submitter Inborn genetic diseases ⚠
- p.Arg279Trp Single submitter Inborn genetic diseases ⚠
- p.Asp104Tyr Single submitter glucocorticoid deficiency 1 ⚠
- p.Asp20His Single submitter Inborn genetic diseases ⚠
- p.Gly160Arg Single submitter Inborn genetic diseases ⚠
- p.Gly162Ser Single submitter Inborn genetic diseases ⚠
- p.Gly262Ser Single submitter glucocorticoid deficiency 1 ⚠
- p.Gly73Asp Single submitter Inborn genetic diseases ⚠
- p.Gly90Ser Single submitter Inborn genetic diseases ⚠
- p.His139Gln Single submitter Inborn genetic diseases ⚠
- p.Ile106Val Single submitter Inborn genetic diseases ⚠
- p.Ile118Val Single submitter Inborn genetic diseases ⚠
- p.Ile154Val Single submitter Inborn genetic diseases ⚠
- p.Ile219Thr Single submitter Inborn genetic diseases ⚠
- p.Ile36Asn Single submitter glucocorticoid deficiency 1 ⚠
- p.Ile82Val Single submitter Inborn genetic diseases ⚠
- p.Ile85Thr Single submitter Inborn genetic diseases ⚠
- p.Lys206Thr Single submitter Inborn genetic diseases ⚠
- p.Met215Lys Single submitter Inborn genetic diseases ⚠
- p.Met255Ile Single submitter glucocorticoid deficiency 1 ⚠
- p.Met266Thr Single submitter Inborn genetic diseases ⚠
- p.Met290Lys Single submitter Inborn genetic diseases
- p.Met290Thr Single submitter Inborn genetic diseases
- p.Met59Val Single submitter Inborn genetic diseases ⚠
- p.Met89Thr Single submitter Inborn genetic diseases ⚠
- p.Ser117Pro Single submitter glucocorticoid deficiency 1 ⚠
- p.Ser169Tyr Single submitter Inborn genetic diseases ⚠
- p.Ser180Leu Single submitter Inborn genetic diseases ⚠
- p.Ser7= Single submitter glucocorticoid deficiency 1
- p.Thr156Met Single submitter Inborn genetic diseases ⚠
- p.Thr159Met Single submitter Inborn genetic diseases ⚠
- p.Thr222= Single submitter glucocorticoid deficiency 1
- p.Thr222Ile Single submitter Inborn genetic diseases ⚠
- p.Tyr276Asp Single submitter ⚠
- p.Val123Met Single submitter Inborn genetic diseases ⚠
- p.Val175Glu Single submitter glucocorticoid deficiency 1 ⚠
- p.Val270Ile Single submitter glucocorticoid deficiency 1 ⚠