Is ABCB4 p.Ala262fs (c.784del) pathogenic?

ABCB4 p.Ala262fs (c.784del) is classified Pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-09). Absent from gnomAD; Associated with progressive familial intrahepatic cholestasis type 3.

What condition is associated with ABCB4 p.Ala262fs (c.784del)?

ABCB4 p.Ala262fs (c.784del) is associated with progressive familial intrahepatic cholestasis type 3 (ClinVar).

How common is ABCB4 p.Ala262fs (c.784del) in the general population?

ABCB4 p.Ala262fs (c.784del) is absent from gnomAD (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

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

ABCB4 p.Ala262fs

c.784del · rs2546854047 · VCV2687821

Pathogenic Single submitter

Classification

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 type 3

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 9.9	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.Ala262fs
Coding: c.784del
MANE Select: NM_000443
dbSNP: rs2546854047
Type: Deletion
Location: chr7:87450017 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 262: 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 type 3 — 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.Asp682fs Pathogenic ★★ same condition
ABCB4 p.Leu518fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Lys1026fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Lys30fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.3081+2_3081+19del Likely pathogenic ★ same condition
ABCB4 p.Ala546fs Pathogenic ★ same condition
ABCB4 p.Gln1257fs Pathogenic ★ same condition
ABCB4 p.His1006fs Likely 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-ala262fs (accessed [today's date]).

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