Is ABCB4 p.Phe210fs (c.628_643del) pathogenic?

ABCB4 p.Phe210fs (c.628643del) is classified Pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Phe210fs (c.628_643del)?

ABCB4 p.Phe210fs (c.628_643del) is associated with familial intrahepatic cholestasis (ClinVar).

ABCB4 p.Phe210fs

c.628_643del · VCV4846443

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ABCB4
Protein: p.Phe210fs
Coding: c.628_643del
MANE Select: NM_000443
Type: Deletion
Location: chr7:87451688 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 210: an α-helix; the abc transmembrane type-1 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

Similar variants

ABCB4 p.Lys1026fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Ser339fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Thr34fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Cys433_Gly434del Uncertain significance ★★ same condition
ABCB4 c.1231-81del Benign ★★ same condition
ABCB4 c.2479-66del Benign ★★ same condition
ABCB4 p.Ala984fs Pathogenic ★ same condition
ABCB4 p.Asn1048fs 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-phe210fs (accessed [today's date]).

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