ABCB1 p.Ala246=
c.738G>A · rs28381867 · VCV736117
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0627%, 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 -11 | GERP -3.7 |
| Overall | ||
| CADD | 6.875 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0627%
African / African-American · 47/74,962 alleles
Filtering AF
0.0484%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0433%
Overall
0.0278%
448/1,613,572 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0627% | 1,595 |
| European (non-Finnish) | 0.0312% | 3,206 |
| Admixed American | 0.0183% | 5,455 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,247 |
| South Asian | 0.0121% | 8,277 |
| Finnishnot grpmax-eligible | 0.00156% | 63,982 |
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
- ABCB1
- Protein
- p.Ala246=
- Coding
- c.738G>A
- MANE Select
- NM_001348946
- dbSNP
- rs28381867
- Type
- single nucleotide variant
- Location
- chr7:87561352 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.72 · 24 PDB
- Residue 246
- the abc transmembrane type-1 1 domain; an α-helix
Similar variants
- ABCB1 c.287-25G>T Benign ★★ same type
- ABCB1 p.Ala1132= Benign/Likely benign ★★ same type
- ABCB1 p.Gln1107Pro Benign/Likely benign ★★ same type
- ABCB1 p.Glu243= Benign/Likely benign ★★ same type
- ABCB1 p.Glu618= Likely benign ★★ same type
- ABCB1 p.Gly412= Benign ★★ same type
- ABCB1 p.Ile1145= Benign ★★ same type
- ABCB1 p.Ile261Val Benign ★★ 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/abcb1-p-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown