ABCC6 (O95255) variants and mutations
ABCC6 (also known as O95255) is a human protein-coding gene encoding an ATP-binding cassette sub-family C member 6 protein. Its ATP-dependent transport activity in liver and other tissues is required indirectly for maintaining extracellular pyrophosphate, a major inhibitor of inappropriate mineralization. Loss-of-function variants cause pseudoxanthoma elasticum and can promote calcification of skin, retina, and arteries. This analysis covers 2,321 ABCC6 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes Pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2, and Generalized arterial calcification of infancy. Example ABCC6 variants include M1?, A2T, and A2V.
Variant analysis overview
- Gene: ABCC6
- Protein: O95255
- UniProt accession: O95255
- Organism: Homo sapiens
- Variants analyzed: 2321
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 2,051 unspecified-consequence records; 112 synonymous variants; 124 missense variants; 17 frameshift variants; 4 in-frame deletions; 7 stop-gained variants; 3 splice-region variants; 1 in-frame insertions; 2 substitution
- Prediction scores: 1,871 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2, Generalized arterial calcification of infancy, autosomal recessive inherited pseudoxanthoma elasticum, pseudoxanthoma elasticum (inherited or acquired), Retinal dystrophy, inherited pseudoxanthoma elasticum, hereditary disease, Abnormality of the eye, nephrolithiasis, bladder calculus, cutis laxa.
Protein structure and variant hotspots
- Protein features: 17 transmembrane segments; 4 domains; 2 binding sites; 2 post-translational modification sites.
- Structural context: 1,817 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, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ABCC6 variants
Examples include M1?, A2T, A2V, A3E, A3S, A3T, P4H, A5P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A2T (p.Ala2Thr), Ensembl rs2049136581, REVEL 0.09, CADD 20.00, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- A2V (p.Ala2Val), TOPMed rs904327622
- A3E (p.Ala3Glu), TOPMed rs2049136227, REVEL 0.06, CADD 15.10
- A3S (p.Ala3Ser), TOPMed rs1461014933, gnomAD rs1461014933, REVEL 0.06, CADD 12.60
- A3T (p.Ala3Thr), TOPMed rs1461014933, gnomAD rs1461014933, REVEL 0.04, CADD 14.60
- P4H (p.Pro4His), rs1555523872, ClinGen CA395202972, ClinVar RCV000499058, UniProt VAR 072803, AlphaMissense 0.11, MetaLR 0.13, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum
- A5P (p.Ala5Pro), TOPMed rs2049135962, REVEL 0.08, CADD 13.60
- A5S (p.Ala5Ser), TOPMed rs2049135962
- E6V (p.Glu6Val), gnomAD rs1044270911, REVEL 0.18, CADD 22.10, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- P7S (p.Pro7Ser), gnomAD rs1472500361, REVEL 0.06, CADD 9.15
- P7T (p.Pro7Thr), gnomAD rs1472500361, REVEL 0.03, CADD 9.18
- C8* (p.Cys8Ter), rs1412967184, ClinGen CA395202921, ClinVar RCV002226612, TOPMed rs1412967184, CADD 27.50, Uncertain significance
- C8G (p.Cys8Gly), TOPMed rs1251550884, REVEL 0.20, CADD 16.60
- C8R (p.Cys8Arg), TOPMed rs1251550884
- A9E (p.Ala9Glu), rs1555523855, ClinGen CA395202916, ClinVar RCV000499275, ClinVar RCV005018854, REVEL 0.05, CADD 7.51, Uncertain significance, Arterial calcification, generalized, of infancy, 2; Autosomal recessive inherite
- G10R (p.Gly10Arg), Ensembl rs2049135225
- G10V (p.Gly10Val), Ensembl rs2049135148
- Q11L (p.Gln11Leu), TOPMed rs1474254372, gnomAD rs1474254372
- Q11R (p.Gln11Arg), TOPMed rs1474254372, gnomAD rs1474254372, REVEL 0.01, CADD 1.13
- G12E (p.Gly12Glu), rs545266923, ClinGen CA279014516, ClinVar RCV002769396, 1000Genomes rs545266923, REVEL 0.02, CADD 0.13, Uncertain significance, Inborn genetic diseases
- G12R (p.Gly12Arg), gnomAD rs1012801593, REVEL 0.03, CADD 9.69, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- Q16* (p.Gln16Ter), rs1555523535, ClinGen CA395202720, ClinVar RCV000499357, Ensembl rs1555523535, Likely pathogenic
- Q16R (p.Gln16Arg), Ensembl rs2049085631
- E18* (p.Glu18Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E18D (p.Glu18Asp), TOPMed rs1238389360, gnomAD rs1238389360, REVEL 0.09, CADD 16.40
- P21S (p.Pro21Ser), rs1235912910, ClinGen CA395202661, ClinVar RCV000499349, UniProt VAR 072805, REVEL 0.03, CADD 6.32, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum
- A22D (p.Ala22Asp), Ensembl rs1567551434, REVEL 0.06, CADD 7.78
- A22V (p.Ala22Val), Ensembl rs1567551434
- A23S (p.Ala23Ser), ESP rs371804833, ExAC rs371804833, TOPMed rs371804833, gnomAD rs371804833, REVEL 0.01, CADD 0.06, Uncertain significance
- A23T (p.Ala23Thr), rs371804833, NCI-TCGA Cosmic COSV9922, cosmic curated COSV99228, ESP rs371804833, REVEL 0.01, CADD 0.18, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- S28G (p.Ser28Gly), Ensembl rs2141227184, REVEL 0.08, CADD 18.20
- S28R (p.Ser28Arg), ExAC rs770233922, TOPMed rs770233922, gnomAD rs770233922, REVEL 0.10, CADD 9.81
- A35T (p.Ala35Thr), gnomAD rs1417615917, REVEL 0.09, CADD 19.00
- G36E (p.Gly36Glu), ExAC rs777330921, TOPMed rs777330921, gnomAD rs777330921, REVEL 0.20, CADD 22.50, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- V37F (p.Val37Phe), rs557779326, ClinGen CA7926719, ClinVar RCV000942182, 1000Genomes rs557779326, REVEL 0.11, CADD 17.60, Likely benign, not provided
- W38S (p.Trp38Ser), rs72653752, ClinGen CA7926718, ClinVar RCV000499269, ClinVar RCV001577317, REVEL 0.66, CADD 26.10, Uncertain significance, not provided
- V39A (p.Val39Ala), TOPMed rs2049083798, REVEL 0.06, CADD 11.50, Uncertain significance, Inborn genetic diseases
- V39I (p.Val39Ile), gnomAD rs1263070594
- P40A (p.Pro40Ala), ExAC rs778544828, TOPMed rs778544828, gnomAD rs778544828, REVEL 0.71, CADD 24.80, Uncertain significance
- P40L (p.Pro40Leu), ExAC rs757143605, gnomAD rs757143605, REVEL 0.72, CADD 26.10
- P40S (p.Pro40Ser), rs778544828, ClinGen CA395202523, cosmic curated COSV10585, ClinVar RCV000499140, REVEL 0.83, CADD 25.30, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum
- P40T (p.Pro40Thr), ExAC rs778544828, TOPMed rs778544828, gnomAD rs778544828, REVEL 0.69, CADD 25.20, Uncertain significance
- P41A (p.Pro41Ala), ExAC rs753761990, TOPMed rs753761990, gnomAD rs753761990, REVEL 0.13, CADD 18.80
- P41L (p.Pro41Leu), ExAC rs777631658, gnomAD rs777631658, REVEL 0.14, CADD 23.60
- P41S (p.Pro41Ser), rs753761990, ClinVar RCV004575104, NCI-TCGA TCGA novel, REVEL 0.09, CADD 19.60, Uncertain significance, not provided
- P41T (p.Pro41Thr), ExAC rs753761990, TOPMed rs753761990, gnomAD rs753761990, REVEL 0.14, CADD 22.60
- M42I (p.Met42Ile), ExAC rs756051632, TOPMed rs756051632, gnomAD rs756051632, REVEL 0.05, CADD 13.30, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- M42L (p.Met42Leu), Ensembl rs1555523458, REVEL 0.02, CADD 1.38
- Y43* (p.Tyr43Ter), NCI-TCGA Cosmic COSV5274, cosmic curated COSV52740, CADD 36.00, Variant assessed as somatic; high impact.
- L44P (p.Leu44Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L44V (p.Leu44Val), rs940803158, ClinGen CA279014406, ClinVar RCV000499271, ClinVar RCV002475997, REVEL 0.33, CADD 26.80, Uncertain significance, Arterial calcification, generalized, of infancy, 2; Autosomal recessive inherite
- V46I (p.Val46Ile), gnomAD rs1425697662, REVEL 0.03, CADD 15.00
- L47F (p.Leu47Phe), NCI-TCGA TCGA novel, Uncertain significance, Inborn genetic diseases
- P49A (p.Pro49Ala), ExAC rs751588595, TOPMed rs751588595, gnomAD rs751588595, REVEL 0.42, CADD 24.30, Uncertain significance, Inborn genetic diseases; Arterial calcification, generalized, of infancy, 2; Pse
- I50V (p.Ile50Val), rs1334507946, ClinGen CA395202401, ClinVar RCV002290093, ClinVar RCV004817006, REVEL 0.02, CADD 10.30, Uncertain significance, Pseudoxanthoma elasticum, forme fruste
- L52H (p.Leu52His), Ensembl rs2049082131
- L53R (p.Leu53Arg), ExAC rs766492973, gnomAD rs766492973, REVEL 0.43, CADD 26.30
- F54L (p.Phe54Leu), ESP rs374115365, TOPMed rs374115365, REVEL 0.09, CADD 22.80
- I55V (p.Ile55Val), ESP rs372062746, ExAC rs372062746, TOPMed rs372062746, gnomAD rs372062746, REVEL 0.04, CADD 13.60, Uncertain significance, Inborn genetic diseases
- H56Q (p.His56Gln), Ensembl rs2049081601, REVEL 0.05, CADD 14.40
- H56R (p.His56Arg), rs367832780, ClinGen CA7926702, ClinVar RCV002983618, ClinVar RCV005021743, REVEL 0.09, CADD 15.00, Uncertain significance, Inborn genetic diseases; Pseudoxanthoma elasticum, forme fruste; Arterial calcif
- H57D (p.His57Asp), TOPMed rs2049081457, REVEL 0.08, CADD 22.20, Uncertain significance, not specified
- H57P (p.His57Pro), 1000Genomes rs374778258, ESP rs374778258, ExAC rs374778258, TOPMed rs374778258, REVEL 0.12, CADD 19.10, Uncertain significance
- H57R (p.His57Arg), 1000Genomes rs374778258, ESP rs374778258, ExAC rs374778258, TOPMed rs374778258, REVEL 0.05, CADD 6.15, Conflicting interpretations, Inborn genetic diseases; Pseudoxanthoma elasticum, forme fruste; Arterial calcif
- H58R (p.His58Arg), TOPMed rs1443741562, REVEL 0.06, CADD 17.00, Uncertain significance, not provided
- R60L (p.Arg60Leu), 1000Genomes rs183648123, ExAC rs183648123, TOPMed rs183648123, gnomAD rs183648123, REVEL 0.09, CADD 19.90, Benign
- R60Q (p.Arg60Gln), rs183648123, ClinGen CA7926695, ClinVar RCV000585541, ClinVar RCV001700226, REVEL 0.03, CADD 16.70, Conflicting interpretations, not provided
- R60W (p.Arg60Trp), ExAC rs761289104, TOPMed rs761289104, gnomAD rs761289104, REVEL 0.08, CADD 23.20
- G61C (p.Gly61Cys), NCI-TCGA Cosmic COSV5274, cosmic curated COSV52748, REVEL 0.23, CADD 23.00, Variant assessed as somatic; moderate impact.
- G61D (p.Gly61Asp), rs72657696, ClinGen CA279014404, ClinVar RCV000499021, UniProt VAR 013364, REVEL 0.35, CADD 24.40, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum
- G61R (p.Gly61Arg), ExAC rs745506209, TOPMed rs745506209, gnomAD rs745506209, REVEL 0.36, CADD 23.10, Uncertain significance
- G61S (p.Gly61Ser), ExAC rs745506209, TOPMed rs745506209, gnomAD rs745506209, REVEL 0.22, CADD 24.10, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum; Pseudoxanthoma elasticum
- Y62C (p.Tyr62Cys), ExAC rs774111532, TOPMed rs774111532, gnomAD rs774111532, REVEL 0.31, CADD 25.40
- L63F (p.Leu63Phe), cosmic curated COSV10506, TOPMed rs978223068, gnomAD rs978223068, REVEL 0.12, CADD 22.70
- L63V (p.Leu63Val), TOPMed rs978223068, gnomAD rs978223068, REVEL 0.04, CADD 18.20, Uncertain significance, Inborn genetic diseases
- R64Q (p.Arg64Gln), rs777566074, ClinGen CA7926690, cosmic curated COSV52745, ClinVar RCV000499118, REVEL 0.06, CADD 18.70, Uncertain significance, Arterial calcification, generalized, of infancy, 2; Autosomal recessive inherite
- R64W (p.Arg64Trp), rs557180313, NCI-TCGA Cosmic COSV5274, cosmic curated COSV52743, UniProt VAR 013365, REVEL 0.34, CADD 29.00, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- S66A (p.Ser66Ala), TOPMed rs1256169470, gnomAD rs1256169470, REVEL 0.23, CADD 25.50
- S66F (p.Ser66Phe), cosmic curated COSV52743, ExAC rs756021073, gnomAD rs756021073, REVEL 0.46, CADD 27.10
- L68F (p.Leu68Phe), ExAC rs748123458, TOPMed rs748123458, gnomAD rs748123458
- L68P (p.Leu68Pro), Ensembl rs1477745192, REVEL 0.64, CADD 29.80
- L68V (p.Leu68Val), ExAC rs748123458, TOPMed rs748123458, gnomAD rs748123458, REVEL 0.22, CADD 24.30
- K70Q (p.Lys70Gln), Ensembl rs1596781321
- A71D (p.Ala71Asp), ExAC rs779991699, gnomAD rs779991699, REVEL 0.25, CADD 24.00
- A71T (p.Ala71Thr), rs1330645129, gnomAD rs1330645129, REVEL 0.04, CADD 16.10, Variant assessed as somatic; moderate impact.
- K72M (p.Lys72Met), gnomAD rs1167869456, REVEL 0.50, CADD 25.70
- K72N (p.Lys72Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M73T (p.Met73Thr), ExAC rs758559224, gnomAD rs758559224, REVEL 0.22, CADD 17.20
- V74E (p.Val74Glu), rs2141220850, ClinGen CA394893688, ClinVar RCV001814661, Ensembl rs2141220850, AlphaMissense 0.66, MetaLR 0.18, Uncertain significance, not provided
- V74M (p.Val74Met), gnomAD rs1426447176, REVEL 0.12, CADD 29.10
- A78S (p.Ala78Ser), 1000Genomes rs2856597, gnomAD rs2856597, REVEL 0.06, CADD 7.38, Uncertain significance, in PXE
- A78T (p.Ala78Thr), rs2856597, ClinGen CA278671597, cosmic curated COSV10940, ClinVar RCV000499196, REVEL 0.03, CADD 8.34, Uncertain significance, Arterial calcification, generalized, of infancy, 2; Autosomal recessive inherite
- L79F (p.Leu79Phe), ExAC rs757533434, gnomAD rs757533434, REVEL 0.19, CADD 23.60
- I80L (p.Ile80Leu), TOPMed rs2049018193
- I80T (p.Ile80Thr), rs754156749, ClinGen CA7926662, ClinVar RCV002911856, ExAC rs754156749, REVEL 0.14, CADD 22.30, Uncertain significance, Inborn genetic diseases
- V81A (p.Val81Ala), gnomAD rs1211998073, REVEL 0.06, CADD 22.90
- L82P (p.Leu82Pro), ExAC rs778282044, gnomAD rs778282044, REVEL 0.44, CADD 26.70
- C83* (p.Cys83Ter), Ensembl rs2141220655
- C83G (p.Cys83Gly), TOPMed rs1289602320
- C83Y (p.Cys83Tyr), TOPMed rs1277521548, gnomAD rs1277521548, REVEL 0.05, CADD 13.10
- S86N (p.Ser86Asn), TOPMed rs1380838743
- S86T (p.Ser86Thr), TOPMed rs1380838743, REVEL 0.02, CADD 12.10
- V87M (p.Val87Met), rs1021031399, ClinGen CA278671556, ClinVar RCV001769436, ClinVar RCV002489802, REVEL 0.06, CADD 20.40, Uncertain significance, not provided; Inborn genetic diseases; Arterial calcification, generalized, of i
- A88V (p.Ala88Val), TOPMed rs2049017340, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- V89D (p.Val89Asp), TOPMed rs1159736192, REVEL 0.14, CADD 22.80
- V89I (p.Val89Ile), gnomAD rs2049017199, REVEL 0.04, CADD 15.40
- A90T (p.Ala90Thr), rs957828732, ClinGen CA278671548, ClinVar RCV000499024, UniProt VAR 072807, REVEL 0.02, CADD 9.82, Uncertain significance, Autosomal recessive inherited pseudoxanthoma elasticum
- A90V (p.Ala90Val), gnomAD rs1339125190, REVEL 0.06, CADD 21.60, Uncertain significance
- Q95* (p.Gln95Ter), Ensembl rs2141220521
- Q95H (p.Gln95His), NCI-TCGA Cosmic COSV9922, cosmic curated COSV99229, Variant assessed as somatic; moderate impact.
- Q95R (p.Gln95Arg), rs1355491834, ClinGen CA394893556, ClinVar RCV002954501, TOPMed rs1355491834, REVEL 0.07, CADD 17.90, Uncertain significance, Inborn genetic diseases
- T98M (p.Thr98Met), cosmic curated COSV99077, gnomAD rs1466913193, REVEL 0.02, CADD 0.01, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- T98P (p.Thr98Pro), Ensembl rs2049016492, REVEL 0.05, CADD 1.25, Uncertain significance, Inborn genetic diseases
- P99L (p.Pro99Leu), gnomAD rs1174296983, REVEL 0.16, CADD 17.70
- E100K (p.Glu100Lys), TOPMed rs1411728572, gnomAD rs1411728572, REVEL 0.09, CADD 11.70
- A101G (p.Ala101Gly), rs753016843, ClinGen CA7926659, ClinVar RCV003361528, ExAC rs753016843, REVEL 0.11, CADD 22.70, Uncertain significance, Inborn genetic diseases
- A101S (p.Ala101Ser), rs756608278, ClinGen CA7926660, ClinVar RCV002680620, ClinVar RCV005021764, REVEL 0.09, CADD 15.80, Conflicting interpretations, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- E103* (p.Glu103Ter), NCI-TCGA Cosmic COSV9922, cosmic curated COSV99229, Variant assessed as somatic; high impact.
- L105F (p.Leu105Phe), NCI-TCGA TCGA novel, Uncertain significance, Inborn genetic diseases
- L105P (p.Leu105Pro), rs1477424498, ClinGen CA394893487, ClinVar RCV003356551, gnomAD rs1477424498, REVEL 0.46, CADD 25.50, Uncertain significance, Inborn genetic diseases
- I106V (p.Ile106Val), TOPMed rs1567549262, gnomAD rs1567549262, REVEL 0.09, CADD 14.10
- H107L (p.His107Leu), TOPMed rs1201921946
- H107R (p.His107Arg), TOPMed rs1201921946
- H107Y (p.His107Tyr), NCI-TCGA TCGA novel, Ensembl rs2049015674, Variant assessed as somatic; moderate impact.
- P108H (p.Pro108His), TOPMed rs1260978010, gnomAD rs1260978010
- P108R (p.Pro108Arg), TOPMed rs1260978010, gnomAD rs1260978010, REVEL 0.37, CADD 24.30
- T109A (p.Thr109Ala), gnomAD rs1033531337, REVEL 0.05, CADD 11.20, Uncertain significance, Inborn genetic diseases
- T109S (p.Thr109Ser), gnomAD rs1183345563, REVEL 0.12, CADD 19.50
- V110M (p.Val110Met), gnomAD rs2049015185, REVEL 0.07, CADD 19.80, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- W111* (p.Trp111Ter), rs1002088882, ClinGen CA278671540, ClinVar RCV000499345, TOPMed rs1002088882, CADD 36.00, Likely pathogenic
- W111C (p.Trp111Cys), TOPMed rs1002088882, gnomAD rs1002088882, Likely pathogenic
- L112I (p.Leu112Ile), Ensembl rs2049014938, REVEL 0.19, CADD 23.00
- T114M (p.Thr114Met), TOPMed rs1441562603, gnomAD rs1441562603, REVEL 0.32, CADD 25.90, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
- T114R (p.Thr114Arg), TOPMed rs1441562603, gnomAD rs1441562603, REVEL 0.49, CADD 25.70, Uncertain significance
- M115L (p.Met115Leu), Ensembl rs2049014583, REVEL 0.20, CADD 23.60
- A118S (p.Ala118Ser), TOPMed rs1052064121, gnomAD rs1052064121
- A118T (p.Ala118Thr), TOPMed rs1052064121, gnomAD rs1052064121, REVEL 0.12, CADD 22.90
- V119A (p.Val119Ala), TOPMed rs2049009427, REVEL 0.06, CADD 17.30, Uncertain significance, Inborn genetic diseases
- F120L (p.Phe120Leu), gnomAD rs1166899687, REVEL 0.16, CADD 19.90
- I122L (p.Ile122Leu), TOPMed rs2049009192
- I122M (p.Ile122Met), gnomAD rs2049009113, REVEL 0.17, CADD 14.20
- I122V (p.Ile122Val), TOPMed rs2049009192, REVEL 0.08, CADD 14.50
- H123R (p.His123Arg), TOPMed rs1424170078, gnomAD rs1424170078, REVEL 0.19, CADD 24.40, Uncertain significance, Inborn genetic diseases
- E125* (p.Glu125Ter), rs879956688, ClinGen CA394893344, ClinVar RCV000499167, gnomAD rs879956688, CADD 36.00, Likely pathogenic, in PXE
- E125K (p.Glu125Lys), rs879956688, ClinGen CA278671493, ClinVar RCV000499366, ClinVar RCV002475990, REVEL 0.43, CADD 25.20, Uncertain significance, Arterial calcification, generalized, of infancy, 2; Autosomal recessive inherite
- R126M (p.Arg126Met), gnomAD rs2049008624, REVEL 0.49, CADD 24.80
- K127* (p.Lys127Ter), 1000Genomes rs2049008560, gnomAD rs2049008560, CADD 36.00
- K127E (p.Lys127Glu), 1000Genomes rs2049008560, gnomAD rs2049008560, REVEL 0.06, CADD 23.10
- K128E (p.Lys128Glu), Ensembl rs1596775875, REVEL 0.21, CADD 24.80
- G129E (p.Gly129Glu), rs72653753, ClinGen CA278671489, ClinVar RCV000499249, ClinVar RCV005641650, REVEL 0.65, CADD 24.50, Uncertain significance, not provided
- V130I (p.Val130Ile), TOPMed rs2049008312
- Q131* (p.Gln131Ter), gnomAD rs1197437569
- Q131R (p.Gln131Arg), rs369280729, ClinGen CA278671485, ClinVar RCV002961283, ClinVar RCV003420482, REVEL 0.03, CADD 15.20, Conflicting interpretations, Inborn genetic diseases; Pseudoxanthoma elasticum, forme fruste; Arterial calcif
- S132L (p.Ser132Leu), 1000Genomes rs545855341, TOPMed rs545855341, REVEL 0.27, CADD 23.70
- S133P (p.Ser133Pro), TOPMed rs989524613, REVEL 0.42, CADD 25.80
- G134V (p.Gly134Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F137L (p.Phe137Leu), gnomAD rs1321662708, REVEL 0.05, CADD 20.60
- G138S (p.Gly138Ser), TOPMed rs1307984851, REVEL 0.09, CADD 22.50
- Y139N (p.Tyr139Asn), gnomAD rs2049007296, REVEL 0.45, CADD 29.30
- W140* (p.Trp140Ter), TOPMed rs1242802005, gnomAD rs1242802005, CADD 37.00
- W140C (p.Trp140Cys), TOPMed rs1242802005, gnomAD rs1242802005, REVEL 0.57, CADD 28.20, Uncertain significance, not provided
- L142F (p.Leu142Phe), gnomAD rs1377884821, REVEL 0.29, CADD 24.70
- C143F (p.Cys143Phe), TOPMed rs1330987157, gnomAD rs1330987157, REVEL 0.14, CADD 23.00, Uncertain significance, ABCC6-related disorder
- V145A (p.Val145Ala), TOPMed rs926414743, gnomAD rs926414743, REVEL 0.10, CADD 19.30
- L146F (p.Leu146Phe), TOPMed rs1480330108, REVEL 0.03, CADD 14.90
- L146S (p.Leu146Ser), ExAC rs761526463, TOPMed rs761526463, gnomAD rs761526463, REVEL 0.17, CADD 19.10, Uncertain significance, Inborn genetic diseases
- P147A (p.Pro147Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P147S (p.Pro147Ser), TOPMed rs980998558, gnomAD rs980998558, REVEL 0.17, CADD 22.80
- P147T (p.Pro147Thr), TOPMed rs980998558, gnomAD rs980998558, REVEL 0.10, CADD 19.10
- A148T (p.Ala148Thr), Ensembl rs2049006458, REVEL 0.06, CADD 15.40
- N150D (p.Asn150Asp), TOPMed rs2049006382
- N150K (p.Asn150Lys), 1000Genomes rs530448710, ExAC rs530448710, TOPMed rs530448710, gnomAD rs530448710, REVEL 0.04, CADD 9.84, Uncertain significance, Inborn genetic diseases
- A151T (p.Ala151Thr), rs1025306917, TOPMed rs1025306917, gnomAD rs1025306917, REVEL 0.02, CADD 0.06, Variant assessed as somatic; moderate impact.
- Q153P (p.Gln153Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q154* (p.Gln154Ter), NCI-TCGA TCGA novel, CADD 36.00, Variant assessed as somatic; high impact.
- Q154P (p.Gln154Pro), 1000Genomes rs563277493, TOPMed rs563277493, gnomAD rs563277493, REVEL 0.20, CADD 17.10
- A155T (p.Ala155Thr), 1000Genomes rs541797555, ExAC rs541797555, gnomAD rs541797555, REVEL 0.03, CADD 15.60
- S156F (p.Ser156Phe), ExAC rs746971185, gnomAD rs746971185
- S156T (p.Ser156Thr), gnomAD rs1177700185, REVEL 0.04, CADD 13.30, Uncertain significance, Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of
Public ABCC6 analysis runs
- ABCC6 analysis run — ABCC6 (2,321 variants) — completed 2026-08-21