ABCC6 p.Arg518=
c.1552C>A · rs72650700 · VCV1952946
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.3 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 12.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/75,012 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000205%
3/1,461,876 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,506 |
| European (non-Finnish) | 8.47e-05% | 1,180,022 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ABCC6
- Protein
- p.Arg518=
- Coding
- c.1552C>A
- MANE Select
- NM_001171
- dbSNP
- rs72650700
- Type
- single nucleotide variant
- Location
- chr16:16190247 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 4 PDB
- Residue 518
- the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in pxe)
Similar variants
- ABCC6 p.Arg518Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ABCC6 p.Arg518Ter Pathogenic ★★ same residue
- ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
- ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
- ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
- ABCC6 c.2787+1G>T Pathogenic ★★ same type
- ABCC6 c.3506+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC6 c.3507-1G>A Pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc6-p-arg518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown