ABCB4 p.Phe269=
c.807C>T · rs1421517860 · VCV514795
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -0.41 | GERP -3.7, phastCons 0.001 |
| Overall | ||
| CADD | 9.962 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,988 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000558%
9/1,613,992 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,996 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| European (non-Finnish) | 0.000339% | 295,004 |
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
- ABCB4
- Protein
- p.Phe269=
- Coding
- c.807C>T
- MANE Select
- NM_000443
- dbSNP
- rs1421517860
- Type
- single nucleotide variant
- Location
- chr7:87449994 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.36 · 4 PDB
- Residue 269
- the abc transmembrane type-1 1 domain
Similar variants
- ABCB4 p.Phe269Leu Uncertain significance ★★ ⚠ same residue
- CROT p.Ile269Asn Uncertain significance ★ ⚠ same residue
- ABCB4 c.1006-2A>C Pathogenic ★★ same type
- ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same type
- ABCB4 c.1560+1G>A Likely pathogenic ★★ same type
- ABCB4 c.2064+3A>T Likely pathogenic ★★ same type
- ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ 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/abcb4-p-phe269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown