ABCG5 p.Pro431=
c.1293G>A · rs765168105 · VCV1769164
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, nfe)
Conditions
2
Cardiovascular phenotype
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 -20 | GERP -3.9 |
| Overall | ||
| CADD | 2.899 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
European (non-Finnish) · 134/1,180,030 alleles
Filtering AF
0.00977%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00912%
Overall
0.00861%
139/1,614,044 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0114% | 8,806 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| East Asian | 0.00446% | 22,444 |
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
- ABCG5
- Protein
- p.Pro431=
- Coding
- c.1293G>A
- MANE Select
- NM_022436
- dbSNP
- rs765168105
- Type
- single nucleotide variant
- Location
- chr2:43823944 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 8 PDB
- Residue 431
- the abc transmembrane type-2 domain; an α-helix
Similar variants
- ABCG5 p.Pro431Arg Uncertain significance ★ ⚠ same residue
- ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
- ABCG5 c.1762+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCG5 c.634+1G>C Likely pathogenic ★★ same condition
- ABCG5 c.904+1G>A Pathogenic ★★ same condition
- ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCG5 p.Arg243Ter Pathogenic ★★ same condition
- ABCG5 p.Arg389His Pathogenic/Likely pathogenic ★★ ⚠ 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/abcg5-p-pro431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown