Is ABCB4 p.Val255fs (c.762del) pathogenic?

ABCB4 p.Val255fs (c.762del) is classified Likely pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). No gnomAD frequency available for this variant; Associated with progressive familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Val255fs (c.762del)?

ABCB4 p.Val255fs (c.762del) is associated with progressive familial intrahepatic cholestasis (ClinVar).

How common is ABCB4 p.Val255fs (c.762del) in the general population?

ABCB4 p.Val255fs (c.762del) is no gnomAD frequency available for this variant (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCB4 p.Val255fs

c.762del · rs2546854192 · VCV2445739

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

progressive 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 8 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCB4
Protein: p.Val255fs
Coding: c.762del
MANE Select: NM_000443
dbSNP: rs2546854192
Type: Deletion
Location: chr7:87450039 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 255: 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

progressive familial intrahepatic cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive familial intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

ABCB4 p.Val255Met Uncertain significance ★★ ⚠ same residue
ABCB4 c.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg176Trp Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Pro479Leu Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Ser320Phe Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Ser978Pro Likely pathogenic ★★ same condition
ABCB4 c.1006-1G>T Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCB4 c.2784-12T>C Conflicting classifications of pathogenicity ★ 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-val255fs (accessed [today's date]).

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