Is ABCB11 p.Arg1001= (c.3003A>G) pathogenic?

ABCB11 p.Arg1001= (c.3003A>G) is classified Likely pathogenic in ABCB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-14). Very rare (popmax 0.00133%, afr); Associated with benign recurrent intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Arg1001= (c.3003A>G)?

ABCB11 p.Arg1001= (c.3003A>G) is associated with benign recurrent intrahepatic cholestasis type 2, progressive familial intrahepatic cholestasis type 2, familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Arg1001= (c.3003A>G) in the general population?

ABCB11 p.Arg1001= (c.3003A>G) is very rare (popmax 0.00133%, afr) (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.Arg1001=

c.3003A>G · rs1691763747 · VCV2681008

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

benign recurrent intrahepatic cholestasis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.77	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.9	GERP 1.9, phastCons 1
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000657% 1/152,160 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.Arg1001=
Coding: c.3003A>G
MANE Select: NM_003742
dbSNP: rs1691763747
Type: single nucleotide variant
Location: chr2:168935237 (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 1001: 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.Arg1001Ter Likely pathogenic ★ same residue
ABCB11 p.Arg1001Thr Uncertain significance ★ ⚠ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+1G>A 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-arg1001 (accessed [today's date]).

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