Is ABCB4 p.Asp682fs (c.2044del) pathogenic?

ABCB4 p.Asp682fs (c.2044del) is classified Pathogenic in ABCB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-08-19). Absent from gnomAD; Associated with progressive familial intrahepatic cholestasis type 3.

How common is ABCB4 p.Asp682fs (c.2044del) in the general population?

ABCB4 p.Asp682fs (c.2044del) 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.Asp682fs

Q: What condition is associated with ABCB4 p.Asp682fs (c.2044del)?

ABCB4 p.Asp682fs (c.2044del) is associated with progressive familial intrahepatic cholestasis type 3, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

c.2044del · rs1562965036 · VCV617459

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 16 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 0.47, phastCons 0.24

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.Asp682fs
Coding: c.2044del
MANE Select: NM_000443
dbSNP: rs1562965036
Type: Deletion
Location: chr7:87426770 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB

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

Also linked: cholestasis, intrahepatic, of pregnancy, 3

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB4 p.Gln458fs 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 p.Ser339fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.3081+2_3081+19del Likely pathogenic ★ same condition
ABCB4 p.Ala198fs Pathogenic ★ same condition
ABCB4 p.Ala262fs 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-asp682fs (accessed [today's date]).

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