CCN6 — 248 ClinVar variants
All ClinVar germline CCN6 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 75 flagged for review →
48 Pathogenic · 10 Pathogenic/Likely pathogenic · 8 Likely pathogenic · 11 Conflicting · 15 Benign · 3 Benign/Likely benign · 86 Likely benign · 67 Uncertain significance
Full CCN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 75
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.
-
CCN6 p.Ala197Pro
Pathogenic/Likely pathogenic
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
Predictors agree, ClinVar conflicts 7
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
CCN6 p.Arg44His
Conflicting
Single submitter
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Arg60His
Conflicting
Single submitter
Inborn genetic diseases
-
CCN6 p.Cys223Arg
Conflicting
Single submitter
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Pro26Leu
Conflicting
Single submitter
Inborn genetic diseases
-
CCN6 p.Pro31Thr
Conflicting
Single submitter
Inborn genetic diseases
-
CCN6 p.Ser7Pro
Conflicting
Single submitter
Inborn genetic diseases
-
CCN6 p.Val104Leu
Conflicting
Single submitter
Inborn genetic diseases
Predictors lean, ClinVar uncertain 40
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
CCN6 p.Ala15Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CCN6 p.Arg199Gly Uncertain significance Multiple submitters
-
CCN6 p.Cys145Tyr
Uncertain significance
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Gln133Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Gln289His
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CCN6 p.Gly112Arg Uncertain significance Multiple submitters
-
CCN6 p.Lys173Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Pro26Ala
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Ala213Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Arg339Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asn308Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Asn308Ser Uncertain significance Single submitter
-
CCN6 p.Asp105Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asp175Asn
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asp28Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asp93His
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Cys100Arg Uncertain significance Single submitter
- CCN6 p.Cys209Ser Uncertain significance Single submitter
-
CCN6 p.Cys285Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Cys75Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Cys75Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Gln2His Uncertain significance Single submitter
- CCN6 p.His128Tyr Uncertain significance Single submitter
-
CCN6 p.His130Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.His49Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Ile157Val Uncertain significance Single submitter
- CCN6 p.Leu185Pro Uncertain significance Single submitter
- CCN6 p.Leu188Ile Uncertain significance Single submitter
-
CCN6 p.Leu274Phe
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Lys208Asn Uncertain significance Single submitter
-
CCN6 p.Lys208Thr
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Pro26Ser Uncertain significance Single submitter
-
CCN6 p.Ser254Asn
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Ser334Thr Uncertain significance Single submitter
- CCN6 p.Thr232Ile Uncertain significance Single submitter
- CCN6 p.Thr29Ile Uncertain significance Single submitter
- CCN6 p.Trp216Cys Uncertain significance Single submitter
- CCN6 p.Tyr109Ser Uncertain significance Single submitter
- CCN6 p.Tyr116Asn Uncertain significance Single submitter
- CCN6 p.Tyr116His Uncertain significance Single submitter
Predictors split 27
The independent predictors disagree with each other — read with care.
-
CCN6 p.Arg44Cys
Likely benign
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Arg60Cys
Benign
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Asp253Asn
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Cys179Gly
Uncertain significance
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Glu123Lys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Gly83Glu
Benign/Likely benign
Multiple submitters
progressive pseudorheumatoid arthropathy of childhood
-
CCN6 p.Lys206Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
CCN6 p.Pro59Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
- CCN6 p.Arg108Ser Uncertain significance Single submitter
-
CCN6 p.Arg221Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asn321Asp
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Asp301Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Gln338Leu Uncertain significance Single submitter
-
CCN6 p.Glu110Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Glu84Lys Uncertain significance Single submitter
- CCN6 p.Gly265Glu Uncertain significance Single submitter
-
CCN6 p.Gly73Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Ile347Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Leu10Pro
Uncertain significance
Single submitter
progressive pseudorheumatoid arthropathy of childhood
- CCN6 p.Leu14Pro Uncertain significance Single submitter
-
CCN6 p.Leu4Phe
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Lys311Glu Uncertain significance Single submitter
-
CCN6 p.Pro154Leu
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Pro55Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
CCN6 p.Ser142Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- CCN6 p.Thr333Ile Uncertain significance Single submitter
- CCN6 p.Val281Ala Uncertain significance Single submitter
All CCN6 variants
Pathogenic 48
- p.Asn178_Cys179insTer Multiple submitters
- p.Cys209fs Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Cys223Gly Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Glu84fs Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ser236fs Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ser39Ter Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ser66Asn Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Trp50Ter Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- c.48+2dup Single submitter progressive pseudorheumatoid arthropathy of childhood
- c.589+1G>A Single submitter progressive pseudorheumatoid arthropathy of childhood
- c.589+2T>C Single submitter
- c.783+1_783+6del Single submitter
- p.Ala15fs Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Cys114Trp Single submitter
- p.Cys238Ter Single submitter
- p.Cys252Ter Single submitter
- p.Cys337_Gln338delinsTer Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Glu243fs Single submitter
- p.Glu32fs Single submitter
- p.Glu37Ter Single submitter
- p.Gly171fs Single submitter
- p.Leu160fs Single submitter
- p.Leu210fs Single submitter
- p.Leu246fs Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Leu27Ter Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Lys207fs Single submitter
- p.Lys208fs Single submitter
- p.Lys208Ter Single submitter
- p.Lys242fs Single submitter
- p.Met1Ile Single submitter
- p.Met1Lys Single submitter
- p.Met1Thr Single submitter
- p.Pro196fs Single submitter
- p.Pro62fs Single submitter
- p.Ser228fs Single submitter
- p.Ser286Ter Single submitter
- p.Ser290fs Single submitter
- p.Ser334Pro Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Thr214fs Single submitter
- p.Thr267fs Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Thr294fs Single submitter Inborn genetic diseases
- p.Trp216fs Single submitter
- p.Tyr109Ter Single submitter
- p.Val38fs Single submitter
- p.Cys78Arg No assertion criteria progressive pseudorheumatoid arthropathy of childhood
- p.Phe280fs No assertion criteria progressive pseudorheumatoid arthropathy of childhood
- p.Trp331Ter No assertion criteria progressive pseudorheumatoid arthropathy of childhood
- p.Val231fs No assertion criteria progressive pseudorheumatoid arthropathy of childhood
Pathogenic/Likely pathogenic 10
- c.49-1G>A Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ala197Pro Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Cys247fs Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Cys337Tyr Multiple submitters Inborn genetic diseases
- p.Cys52Ter Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Cys78Tyr Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Gln289fs Multiple submitters CCN6-related disorder
- p.Leu14fs Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Met1Val Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Tyr99_Cys100delinsPheSer Multiple submitters progressive pseudorheumatoid arthropathy of childhood
Likely pathogenic 8
- c.590-1G>C Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- c.49-763G>T Single submitter
- p.Cys145Arg Single submitter
- p.Cys299Ter Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Leu246Pro Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Pro26fs Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Tyr116Ter Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Cys100Ser No assertion criteria progressive pseudorheumatoid arthropathy of childhood
Conflicting classifications of pathogenicity 11
- c.48+13C>T Single submitter progressive pseudorheumatoid arthropathy of childhood
- c.589+27C>T Single submitter
- c.783+14A>G Single submitter progressive pseudorheumatoid arthropathy of childhood
- p.Arg44His Single submitter progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Arg60His Single submitter Inborn genetic diseases ⚠
- p.Cys223Arg Single submitter progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Gly73= Single submitter
- p.Pro26Leu Single submitter Inborn genetic diseases ⚠
- p.Pro31Thr Single submitter Inborn genetic diseases ⚠
- p.Ser7Pro Single submitter Inborn genetic diseases ⚠
- p.Val104Leu Single submitter Inborn genetic diseases ⚠
Benign 15
- c.346+20C>T Multiple submitters
- c.-254A>G Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ala79= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Arg60Cys Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Cys122= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Gln269= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Gln56His Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Ile298Leu Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Pro26= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Thr24= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- c.346+60C>T Single submitter
- c.48+36G>A Single submitter
- c.590-131G>A Single submitter
- c.590-7G>C Single submitter
- c.784-87C>T Single submitter
Benign/Likely benign 3
- p.Asn178Ile Multiple submitters progressive pseudorheumatoid arthropathy of childhood
- p.Gly83Glu Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Tyr109= Multiple submitters progressive pseudorheumatoid arthropathy of childhood
Likely benign 86
- c.48+229G>A Multiple submitters
- c.784-9T>C Multiple submitters
- p.Arg44Cys Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Cys268= Multiple submitters
- c.346+16T>C Single submitter
- c.346+17G>A Single submitter
- c.346+8TCT[2] Single submitter
- c.347-10C>T Single submitter
- c.347-15C>G Single submitter
- c.347-16T>C Single submitter
- c.347-4T>C Single submitter
- c.48+10C>G Single submitter
- c.48+17G>A Single submitter
- c.48+7C>T Single submitter
- c.48+8C>T Single submitter
- c.49-13T>G Single submitter
- c.49-14A>G Single submitter
- c.49-19C>A Single submitter
- c.49-763G>A Single submitter
- c.49-763G>C Single submitter
- c.49-7A>G Single submitter
- c.49-9C>A Single submitter
- c.589+19A>G Single submitter
- c.589+20T>C Single submitter
- c.589+7A>G Single submitter
- c.590-11C>T Single submitter
- c.590-19T>C Single submitter
- c.590-6T>C Single submitter
- c.590-9T>C Single submitter
- c.783+12A>G Single submitter
- c.783+22_783+26del Single submitter
- c.784-10A>G Single submitter
- c.784-19A>C Single submitter
- c.784-19A>G Single submitter
- c.784-20C>T Single submitter
- c.784-6T>G Single submitter
- p.Ala119= Single submitter
- p.Asn321= Single submitter
- p.Asp28= Single submitter
- p.Asp70= Single submitter
- p.Asp90= Single submitter
- p.Cys252= Single submitter
- p.Cys285= Single submitter
- p.Cys304= Single submitter
- p.Cys52= Single submitter
- p.Gln126= Single submitter
- p.Gln289= Single submitter
- p.Glu182= Single submitter
- p.Glu37= Single submitter
- p.Gly151= Single submitter
- p.Gly25= Single submitter
- p.Gly3= Single submitter
- p.Gly71= Single submitter
- p.His49= Single submitter
- p.Ile306= Single submitter
- p.Leu10= Single submitter
- p.Leu11= Single submitter
- p.Leu246= Single submitter
- p.Leu330= Single submitter
- p.Leu354= Single submitter
- p.Leu5= Single submitter
- p.Lys172= Single submitter
- p.Lys244= Single submitter
- p.Lys302= Single submitter
- p.Lys309= Single submitter
- p.Pro263= Single submitter
- p.Pro307= Single submitter
- p.Pro31= Single submitter
- p.Pro55= Single submitter
- p.Pro82= Single submitter
- p.Ser103= Single submitter
- p.Ser177= Single submitter
- p.Ser310= Single submitter
- p.Ser39= Single submitter
- p.Thr194= Single submitter
- p.Thr222= Single submitter
- p.Thr259= Single submitter
- p.Thr30= Single submitter
- p.Thr333= Single submitter
- p.Trp50Arg Single submitter
- p.Tyr198= Single submitter
- p.Val127= Single submitter
- p.Val336= Single submitter
- p.Val38= Single submitter
- p.Val38Ala Single submitter Inborn genetic diseases
- p.Val65= Single submitter
Uncertain significance 67
- p.Ala15Thr Multiple submitters Inborn genetic diseases ⚠
- p.Arg199Gly Multiple submitters ⚠
- p.Asp253Asn Multiple submitters Inborn genetic diseases ⚠
- p.Cys145Tyr Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Cys179Gly Multiple submitters progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Gln133Glu Multiple submitters Inborn genetic diseases ⚠
- p.Gln289His Multiple submitters Inborn genetic diseases ⚠
- p.Glu123Lys Multiple submitters Inborn genetic diseases ⚠
- p.Gly112Arg Multiple submitters ⚠
- p.Lys173Glu Multiple submitters Inborn genetic diseases ⚠
- p.Lys206Glu Multiple submitters Inborn genetic diseases ⚠
- p.Pro26Ala Multiple submitters Inborn genetic diseases ⚠
- p.Pro59Ser Multiple submitters Inborn genetic diseases ⚠
- c.346+5G>A Single submitter progressive pseudorheumatoid arthropathy of childhood
- c.347-10_347-6del Single submitter
- p.Ala213Thr Single submitter Inborn genetic diseases ⚠
- p.Arg108Ser Single submitter ⚠
- p.Arg221Ile Single submitter Inborn genetic diseases ⚠
- p.Arg339Gly Single submitter Inborn genetic diseases ⚠
- p.Arg342fs Single submitter
- p.Asn308Lys Single submitter Inborn genetic diseases ⚠
- p.Asn308Ser Single submitter ⚠
- p.Asn321Asp Single submitter Inborn genetic diseases ⚠
- p.Asp105Val Single submitter Inborn genetic diseases ⚠
- p.Asp175Asn Single submitter Inborn genetic diseases ⚠
- p.Asp28Gly Single submitter Inborn genetic diseases ⚠
- p.Asp301Gly Single submitter Inborn genetic diseases ⚠
- p.Asp93His Single submitter Inborn genetic diseases ⚠
- p.Cys100Arg Single submitter ⚠
- p.Cys209Ser Single submitter ⚠
- p.Cys285Tyr Single submitter Inborn genetic diseases ⚠
- p.Cys75Gly Single submitter Inborn genetic diseases ⚠
- p.Cys75Tyr Single submitter Inborn genetic diseases ⚠
- p.Gln2His Single submitter ⚠
- p.Gln338Leu Single submitter ⚠
- p.Glu110Lys Single submitter Inborn genetic diseases ⚠
- p.Glu84Lys Single submitter ⚠
- p.Gly265Glu Single submitter ⚠
- p.Gly73Arg Single submitter Inborn genetic diseases ⚠
- p.His128Tyr Single submitter ⚠
- p.His130Arg Single submitter Inborn genetic diseases ⚠
- p.His49Arg Single submitter Inborn genetic diseases ⚠
- p.Ile157Val Single submitter ⚠
- p.Ile347Thr Single submitter Inborn genetic diseases ⚠
- p.Leu10Pro Single submitter progressive pseudorheumatoid arthropathy of childhood ⚠
- p.Leu14Pro Single submitter ⚠
- p.Leu185Pro Single submitter ⚠
- p.Leu188Ile Single submitter ⚠
- p.Leu274Phe Single submitter Inborn genetic diseases ⚠
- p.Leu4Phe Single submitter Inborn genetic diseases ⚠
- p.Lys208Asn Single submitter ⚠
- p.Lys208Thr Single submitter Inborn genetic diseases ⚠
- p.Lys311Glu Single submitter ⚠
- p.Pro154Leu Single submitter Inborn genetic diseases ⚠
- p.Pro26Ser Single submitter ⚠
- p.Pro55Arg Single submitter Inborn genetic diseases ⚠
- p.Ser142Gly Single submitter Inborn genetic diseases ⚠
- p.Ser254Asn Single submitter Inborn genetic diseases ⚠
- p.Ser334Thr Single submitter ⚠
- p.Thr232Ile Single submitter ⚠
- p.Thr29Ile Single submitter ⚠
- p.Thr333Ile Single submitter ⚠
- p.Trp216Cys Single submitter ⚠
- p.Tyr109Ser Single submitter ⚠
- p.Tyr116Asn Single submitter ⚠
- p.Tyr116His Single submitter ⚠
- p.Val281Ala Single submitter ⚠