Is ABCB11 p.Asp848fs (c.2542del) pathogenic?

ABCB11 p.Asp848fs (c.2542del) is classified Pathogenic/Likely pathogenic in ABCB11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-14). Very rare (popmax 8.48e-05%, nfe); Associated with benign recurrent intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Asp848fs (c.2542del)?

ABCB11 p.Asp848fs (c.2542del) is associated with benign recurrent intrahepatic cholestasis type 2, progressive familial intrahepatic cholestasis type 2, familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Asp848fs (c.2542del) in the general population?

ABCB11 p.Asp848fs (c.2542del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

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.Asp848fs

c.2542del · rs1692220779 · VCV2678310

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 7.8	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,210 alleles

Overall 6.85e-05% 1/1,460,728 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCB11
Protein: p.Asp848fs
Coding: c.2542del
MANE Select: NM_003742
dbSNP: rs1692220779
Type: Deletion
Location: chr2:168944673 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 848: an α-helix; the abc transmembrane type-1 2 domain

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 familial intrahepatic cholestasis

For Benign recurrent intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ABCB11 p.Asp848Asn Uncertain significance ★ ⚠ same residue
ABCB11 c.3213+1del Pathogenic ★★ same condition
ABCB11 p.Arg830fs Pathogenic ★★ same condition
ABCB11 p.Asn199fs 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

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-asp848fs (accessed [today's date]).

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