Is ABCB11 p.Phe682fs (c.2044_2062del) pathogenic?

ABCB11 p.Phe682fs (c.20442062del) is classified Likely pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). Associated with benign recurrent intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Phe682fs (c.2044_2062del)?

ABCB11 p.Phe682fs (c.2044_2062del) is associated with benign recurrent intrahepatic cholestasis type 2, progressive familial intrahepatic cholestasis type 2 (ClinVar).

How is Benign recurrent intrahepatic cholestasis inherited?

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

ABCB11 p.Phe682fs

c.2044_2062del · VCV3584653

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

benign recurrent intrahepatic cholestasis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.3	GERP -4.2

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

Variant & gene context

Gene: ABCB11
Protein: p.Phe682fs
Coding: c.2044_2062del
MANE Select: NM_003742
Type: Deletion
Location: chr2:168968440 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

benign recurrent intrahepatic cholestasis type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive familial intrahepatic cholestasis type 2

For Benign recurrent intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ABCB11 p.Arg830fs Pathogenic ★★ same condition
ABCB11 p.Asn199fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Asp848fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Gln1058fs Pathogenic ★★ same condition
ABCB11 p.Gly1267fs Likely pathogenic ★★ same condition
ABCB11 p.Gly648fs Pathogenic ★★ same condition
ABCB11 p.His717fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Ile1061fs 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/abcb11-p-phe682fs (accessed [today's date]).

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