Is ABCB4 p.Ala1047Pro (c.3139G>C) pathogenic?

ABCB4 p.Ala1047Pro (c.3139G>C) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). AlphaMissense: likely benign (0.0628); Absent from gnomAD v4.1; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Ala1047Pro (c.3139G>C)?

ABCB4 p.Ala1047Pro (c.3139G>C) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB4 p.Ala1047Pro (c.3139G>C) in the general population?

ABCB4 p.Ala1047Pro (c.3139G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB4 p.Ala1047Pro (c.3139G>C)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

ABCB4 p.Ala1047Pro

c.3139G>C · VCV4846381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -3.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP 0.13, phastCons 0.47
Regional constraint	o/e 0.77	unconstrained · MANE · 14 kb · p 8.2e-06 · regional, not allelic
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ala1047Pro
Coding: c.3139G>C
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87408177 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 1047: a turn; the abc transporter 2 domain

Full ABCB4 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

ABCB4 p.Ala1047fs Pathogenic ★★ same residue
ABCB4 p.Ala1047= Likely benign ★ same residue
ABCB4 c.2064+3A>T Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3081+1G>C 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-ala1047pro (accessed [today's date]).

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