Is ABCB11 p.Leu232= (c.696G>T) pathogenic?

ABCB11 p.Leu232= (c.696G>T) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-14). Very rare (popmax 0.00908%, nfe); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Leu232= (c.696G>T)?

ABCB11 p.Leu232= (c.696G>T) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Leu232= (c.696G>T) in the general population?

ABCB11 p.Leu232= (c.696G>T) is very rare (popmax 0.00908%, nfe) (gnomAD).

ABCB11 p.Leu232=

c.696G>T · rs11568358 · VCV1154715

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00908%, nfe)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.85	GERP -0.87, phastCons 0.25
Overall
CADD	15.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00908% European (non-Finnish) · 107/1,178,636 alleles

Filtering AF 0.00767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00709%

Overall 0.00701% 113/1,611,368 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00908%	11,015
Remaining individualsnot grpmax-eligible	0.00481%	20,773
African / African-American	0.00267%	37,409
South Asian	0.0011%	90,774

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.Leu232=
Coding: c.696G>T
MANE Select: NM_003742
dbSNP: rs11568358
Type: single nucleotide variant
Location: chr2:168993798 (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 232: an α-helix; the abc transmembrane type-1 1 domain

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.Leu232fs Pathogenic/Likely pathogenic ★★ 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-leu232 (accessed [today's date]).

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