Is ABCB11 p.Pro740fs (c.2219del) pathogenic?

ABCB11 p.Pro740fs (c.2219del) is classified Pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Pro740fs (c.2219del)?

ABCB11 p.Pro740fs (c.2219del) is associated with familial intrahepatic cholestasis (ClinVar).

ABCB11 p.Pro740fs

c.2219del · VCV4846116

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -2

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

Variant & gene context

Gene: ABCB11
Protein: p.Pro740fs
Coding: c.2219del
MANE Select: NM_003742
Type: Deletion
Location: chr2:168958088 (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 740: an α-helix

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

Disease context

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

Similar variants

ABCB11 c.3213+1del Pathogenic ★★ same condition
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.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-pro740fs (accessed [today's date]).

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