ABCB6 p.Ala373=
c.1119G>A · rs752219177 · VCV1346286
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0303%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.103 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.45 | GERP -4.4, phastCons 0.99 |
| Overall | ||
| CADD | 10.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0303%
Admixed American · 18/59,442 alleles
Filtering AF
0.0196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0161%
Overall
0.00325%
52/1,601,672 alleles · ultra-rare
exomes 49/1,449,518 · genomes 3/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0303% | 3,302 |
| Middle Eastern | 0.0178% | 5,606 |
| South Asian | 0.00333% | 30,061 |
| Remaining individualsnot grpmax-eligible | 0.00324% | 30,896 |
| European (non-Finnish) | 0.00239% | 41,882 |
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
- ABCB6
- Protein
- p.Ala373=
- Coding
- c.1119G>A
- MANE Select
- NM_005689
- dbSNP
- rs752219177
- Type
- single nucleotide variant
- Location
- chr2:219216032 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.17 · 16 PDB
- Residue 373
- the abc transmembrane type-1 domain; an α-helix
Similar variants
- ABCB6 p.Ala373Val Uncertain significance ★ ⚠ same residue
- ABCB6 p.Ala164Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala681Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Arg135Ser Uncertain significance ★★ ⚠ same type
- ABCB6 p.Arg439Cys Uncertain significance ★★ ⚠ same type
- ABCB6 p.Arg450Gln Uncertain significance ★★ ⚠ 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/abcb6-p-ala373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown