Is ABCB4 p.Arg47Ter (c.139C>T) pathogenic?

ABCB4 p.Arg47Ter (c.139C>T) is classified Pathogenic in ABCB4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-14). Very rare (popmax 0.00223%, eas); Associated with ABCB4-related disorder.

What condition is associated with ABCB4 p.Arg47Ter (c.139C>T)?

ABCB4 p.Arg47Ter (c.139C>T) is associated with ABCB4-related disorder, gallbladder disease 1, familial intrahepatic cholestasis (ClinVar).

How common is ABCB4 p.Arg47Ter (c.139C>T) in the general population?

ABCB4 p.Arg47Ter (c.139C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ABCB4 p.Arg47Ter

c.139C>T · rs376926391 · VCV502776

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

ABCB4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 28
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.62 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 1, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,852 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000868% 14/1,612,712 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
South Asian	0.0022%	45,486
Remaining individualsnot grpmax-eligible	0.0016%	62,442
African / African-American	0.00134%	74,732
European (non-Finnish)	0.000763%	131,035

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.Arg47Ter
Coding: c.139C>T
MANE Select: NM_000443
dbSNP: rs376926391
Type: single nucleotide variant
Location: chr7:87462905 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 47: a turn; a UniProt-annotated variant site (in gbd1; partly retained intracellularly; reduces efflux activity for pc in a phosphorylation-dependent manner); a UniProt-annotated variant site (found in patients with cholangitis; uncertain significance)

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCB4-related disorder

Also linked: gallbladder disease 1 familial intrahepatic cholestasis

Similar variants

ABCB4 p.Arg47Gly Likely pathogenic ★ ⚠ same residue
ABCB4 p.Arg47Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB4 p.Arg47= Uncertain significance ★ same residue
ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2064+3A>T Likely pathogenic ★★ same condition
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2783+1G>T 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/abcb4-p-arg47ter (accessed [today's date]).

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