Is ABCB11 p.Arg44fs (c.132_133del) pathogenic?

ABCB11 p.Arg44fs (c.132133del) is classified Pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Absent from gnomAD; Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Arg44fs (c.132_133del)?

ABCB11 p.Arg44fs (c.132_133del) is associated with progressive familial intrahepatic cholestasis type 2, benign recurrent intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Arg44fs (c.132_133del) in the general population?

ABCB11 p.Arg44fs (c.132_133del) 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.

ABCB11 p.Arg44fs

c.132_133del · rs2545487249 · VCV3068715

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 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 11	GERP 1.8, 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: ABCB11
Protein: p.Arg44fs
Coding: c.132_133del
MANE Select: NM_003742
dbSNP: rs2545487249
Type: Microsatellite
Location: chr2:169014320 (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

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

Also linked: benign recurrent intrahepatic cholestasis type 2

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB11 p.Arg44Thr Uncertain significance ⚠ same residue
ABCB11 p.Ile610fs Pathogenic ★★ same condition
ABCB11 p.Leu1219_Ser1220insTer Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Pro378fs Likely pathogenic ★★ same condition
ABCB11 p.Thr812fs Likely pathogenic ★ same condition
ABCB11 p.Arg44= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1198-1G>C 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-arg44fs (accessed [today's date]).

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