ABCB11 p.Phe508=
c.1524C>T · rs780698425 · VCV1123453
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -0.58, phastCons 1 |
| Overall | ||
| CADD | 12.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,068 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.000744%
12/1,612,936 alleles · ultra-rare
exomes 10/1,460,930 · genomes 2/152,006 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,279 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,402 |
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
- ABCB11
- Protein
- p.Phe508=
- Coding
- c.1524C>T
- MANE Select
- NM_003742
- dbSNP
- rs780698425
- Type
- single nucleotide variant
- Location
- chr2:168971961 (GRCh38)
- Gene constraint
- LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.23 · 9 PDB
- Residue 508
- the abc transporter 1 domain
Similar variants
- ABCB11 p.Phe508Ser Uncertain significance ★ ⚠ same residue
- ABCB11 p.Phe508fs Pathogenic ★ same residue
- ABCB11 c.1084-2A>G Pathogenic ★★ same type
- ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.1198-2A>C Likely pathogenic ★★ same type
- ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.150+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/abcb11-p-phe508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown