ABCG8 p.Ala422=
c.1266G>A · rs567600982 · VCV1764256
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
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 -8.9 | GERP -2.8 |
| Overall | ||
| CADD | 0.184 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,978 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00161%
26/1,613,830 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,989 |
| Finnishnot grpmax-eligible | 0.00313% | 31,998 |
| South Asian | 0.0022% | 45,526 |
| European (non-Finnish) | 0.00161% | 62,105 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- ABCG8
- Protein
- p.Ala422=
- Coding
- c.1266G>A
- MANE Select
- NM_022437
- dbSNP
- rs567600982
- Type
- single nucleotide variant
- Location
- chr2:43873841 (GRCh38)
- Gene constraint
- LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 8 PDB
- Residue 422
- the abc transmembrane type-2 domain; an α-helix
Similar variants
- ABCG8 p.Ala422Val Uncertain significance ★ ⚠ same residue
- ABCG8 p.Arg121Ter Pathogenic ★★ same condition
- ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ABCG8 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCG8 p.Ala248Thr Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala346Thr Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala449Val Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala450Thr Uncertain significance ★★ ⚠ 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/abcg8-p-ala422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown