Is ABCB11 p.Arg33= (c.97A>C) pathogenic?

ABCB11 p.Arg33= (c.97A>C) is classified Likely benign in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). Very rare (popmax 0.00342%, amr); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Arg33= (c.97A>C)?

ABCB11 p.Arg33= (c.97A>C) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Arg33= (c.97A>C) in the general population?

ABCB11 p.Arg33= (c.97A>C) is very rare (popmax 0.00342%, amr) (gnomAD).

ABCB11 p.Arg33=

c.97A>C · VCV4846154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00342%, amr)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.81	GERP -0.6, phastCons 0.9
Overall
CADD	13.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00342% Admixed American · 2/58,532 alleles

Filtering AF 0.000567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000125% 2/1,597,514 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.Arg33=
Coding: c.97A>C
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:169016779 (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 33: the 'disordered' region

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 p.Arg33Ser 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.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>C Likely pathogenic ★★ same condition
ABCB11 c.2012-2A>G 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-arg33 (accessed [today's date]).

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