Is ABCB11 p.Gln159= (c.477A>G) pathogenic?

ABCB11 p.Gln159= (c.477A>G) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0711%, afr); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Gln159= (c.477A>G)?

ABCB11 p.Gln159= (c.477A>G) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Gln159= (c.477A>G) in the general population?

ABCB11 p.Gln159= (c.477A>G) is ultra-rare (popmax 0.0711%, afr) (gnomAD).

ABCB11 p.Gln159=

c.477A>G · rs191042013 · VCV501424

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0711%, afr)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -2.2, phastCons 1
Overall
CADD	8.164	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0711% African / African-American · 51/71,764 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0499%

Overall 0.00485% 73/1,505,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0711%	1,407
Middle Eastern	0.035%	2,854
Admixed American	0.00979%	10,214
Remaining individualsnot grpmax-eligible	0.0052%	19,227
European (non-Finnish)	0.00108%	92,985

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.Gln159=
Coding: c.477A>G
MANE Select: NM_003742
dbSNP: rs191042013
Type: single nucleotide variant
Location: chr2:168996635 (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 159: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial intrahepatic cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>C Likely pathogenic ★★ same condition
ABCB11 c.2012-2A>G Pathogenic ★★ same condition
ABCB11 c.2012-8T>G Pathogenic/Likely pathogenic ★★ 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/abcb11-p-gln159 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown