Is ABCB4 p.Ala1090Pro (c.3268G>C) pathogenic?

ABCB4 p.Ala1090Pro (c.3268G>C) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-10). AlphaMissense: ambiguous (0.5389); Very rare (popmax 8.47e-05%, nfe).

How common is ABCB4 p.Ala1090Pro (c.3268G>C) in the general population?

ABCB4 p.Ala1090Pro (c.3268G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCB4 p.Ala1090Pro (c.3268G>C)?

AlphaMissense predicts ambiguous (score 0.5389) — an in-silico prediction, not a clinical call.

ABCB4 p.Ala1090Pro

c.3268G>C · rs1562950481 · VCV596842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5389 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5389	ambiguous
REVEL	0.409	indeterminate
SaProt	LLR -12.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.35	GERP -2
Regional constraint	o/e 0.77	unconstrained · MANE · 14 kb · p 8.2e-06 · regional, not allelic
Overall
CADD	12.13	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,536 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.Ala1090Pro
Coding: c.3268G>C
MANE Select: NM_000443
dbSNP: rs1562950481
Type: single nucleotide variant
Location: chr7:87408048 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 1090: the abc transporter 2 domain

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

Similar variants

ABCB4 p.Ala1090= Likely benign ★ same residue
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

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-ala1090pro (accessed [today's date]).

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