Is ABCB4 p.Ala979Glu (c.2936C>A) pathogenic?

ABCB4 p.Ala979Glu (c.2936C>A) is classified Uncertain significance in ABCB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-24). AlphaMissense: likely pathogenic (0.9783); Very rare (popmax 0.00534%, afr).

How common is ABCB4 p.Ala979Glu (c.2936C>A) in the general population?

ABCB4 p.Ala979Glu (c.2936C>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ABCB4 p.Ala979Glu (c.2936C>A)?

AlphaMissense predicts likely pathogenic (score 0.9783) — an in-silico prediction, not a clinical call.

ABCB4 p.Ala979Glu

c.2936C>A · rs374711909 · VCV596624

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9783	likely pathogenic · top 6% in ABCB4
REVEL	0.759	pathogenic-leaning
SaProt	LLR -12.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 14 kb · p 8.2e-06 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00534% African / African-American · 4/74,922 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/152,156 alleles · very rare

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.Ala979Glu
Coding: c.2936C>A
MANE Select: NM_000443
dbSNP: rs374711909
Type: single nucleotide variant
Location: chr7:87409381 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 979: an α-helix; the abc transmembrane type-1 2 domain

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

Similar variants

ABCB4 c.1006-2A>C Pathogenic ★★ same type
ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.1560+1G>A Likely pathogenic ★★ same type
ABCB4 c.2064+3A>T Likely pathogenic ★★ same type
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.286+1G>A 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/abcb4-p-ala979glu (accessed [today's date]).

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