Is ABCB4 p.Arg47Gly (c.139C>G) pathogenic?

ABCB4 p.Arg47Gly (c.139C>G) is classified Likely pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). AlphaMissense: ambiguous (0.5281); Absent from gnomAD v4.1; Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Arg47Gly (c.139C>G)?

ABCB4 p.Arg47Gly (c.139C>G) is associated with gallbladder disease 1 (ClinVar).

How common is ABCB4 p.Arg47Gly (c.139C>G) in the general population?

ABCB4 p.Arg47Gly (c.139C>G) is absent from gnomAD v4.1 (gnomAD).

How is Low phospholipid-associated cholelithiasis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCB4 p.Arg47Gly (c.139C>G)?

AlphaMissense predicts ambiguous (score 0.5281) — an in-silico prediction, not a clinical call.

ABCB4 p.Arg47Gly

c.139C>G · VCV4846605

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

gallbladder disease 1

Computational evidence

Protein change
AlphaMissense	0.5281	ambiguous
REVEL	0.764	pathogenic-leaning
SaProt	LLR -10.65	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
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
Regional constraint	o/e 1.05	unconstrained · MANE · 13 kb · p 0.67 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB4
Protein: p.Arg47Gly
Coding: c.139C>G
MANE Select: NM_000443
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

gallbladder disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Low phospholipid-associated cholelithiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult

Similar variants

ABCB4 p.Arg47Ter 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.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3486+1G>A 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-arg47gly (accessed [today's date]).

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