Is ABCB4 p.Gln458= (c.1374G>A) pathogenic?

ABCB4 p.Gln458= (c.1374G>A) is classified Likely benign in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). Absent from gnomAD v4.1; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Gln458= (c.1374G>A)?

ABCB4 p.Gln458= (c.1374G>A) is associated with familial intrahepatic cholestasis, gallbladder disease 1 (ClinVar).

How common is ABCB4 p.Gln458= (c.1374G>A) in the general population?

ABCB4 p.Gln458= (c.1374G>A) is absent from gnomAD v4.1 (gnomAD).

ABCB4 p.Gln458=

c.1374G>A · rs267601610 · VCV4846585

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -1.1, phastCons 0.78
Overall
CADD	6.458	PHRED · no single calibrated threshold — expert panels disagree

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.Gln458=
Coding: c.1374G>A
MANE Select: NM_000443
dbSNP: rs267601610
Type: single nucleotide variant
Location: chr7:87440385 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 458: the abc transporter 1 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

Also linked: gallbladder disease 1

Similar variants

ABCB4 p.Gln458Pro Uncertain significance ★★ ⚠ same residue
ABCB4 p.Gln458fs Pathogenic ★★ 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
ABCB4 c.286+1G>A 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-gln458 (accessed [today's date]).

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