Is ABCB11 p.Gln794Arg (c.2381A>G) pathogenic?

ABCB11 p.Gln794Arg (c.2381A>G) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.0914); Very rare (popmax 0.00235%, eas); Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Gln794Arg (c.2381A>G)?

ABCB11 p.Gln794Arg (c.2381A>G) is associated with progressive familial intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Gln794Arg (c.2381A>G) in the general population?

ABCB11 p.Gln794Arg (c.2381A>G) is very rare (popmax 0.00235%, eas) (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCB11 p.Gln794Arg (c.2381A>G)?

AlphaMissense predicts likely benign (score 0.0914) — an in-silico prediction, not a clinical call.

ABCB11 p.Gln794Arg

c.2381A>G · VCV3779988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00235%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

progressive familial intrahepatic cholestasis type 2

Computational evidence

Protein change
AlphaMissense	0.0914	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -4.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.9, phastCons 1
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00235% East Asian · 1/42,618 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000438%

Overall 0.000918% 13/1,416,246 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00235%	42,618
European (non-Finnish)	0.00104%	96,273

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.Gln794Arg
Coding: c.2381A>G
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168944924 (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 794: 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

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

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB11 p.Gln794Ter Pathogenic ★★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.150+2T>C 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.1810-1G>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-gln794arg (accessed [today's date]).

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