ABCC6 p.Arg600His
c.1799G>A · rs761433545 · VCV1521281
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2824 | likely benign |
|---|---|---|
| REVEL | 0.887 | moderately pathogenic-leaning |
| SaProt | LLR -11.63 | damaging |
| ⇒ REVEL and SaProt call this damaging; AlphaMissense does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,757 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,231 |
| Admixed American | 0.00167% | 59,956 |
| European (non-Finnish) | 0.000848% | 117,979 |
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.Arg600His
- Coding
- c.1799G>A
- MANE Select
- NM_001171
- dbSNP
- rs761433545
- Type
- single nucleotide variant
- Location
- chr16:16187192 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 4 PDB
- Residue 600
- a UniProt-annotated variant site (in pxe)
Similar variants
- ABCC6 p.Arg600Cys Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ABCC6 p.Arg600Pro Pathogenic ★ same residue
- ABCC6 p.Arg600Leu Uncertain significance ⚠ same residue
- ABCC6 c.3883-6G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCC6 p.Gly755Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ABCC6 p.Arg1414His Uncertain significance ★★ ⚠ same condition
- ABCC6 p.Gly1327Arg Uncertain significance ★★ ⚠ same condition
- ABCC6 p.Arg391Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
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-arg600his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown