Is ABCB11 p.Arg52Gln (c.155G>A) pathogenic?

ABCB11 p.Arg52Gln (c.155G>A) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-21). AlphaMissense: likely benign (0.1327); Ultra-rare (popmax 0.0165%, mid); Associated with ABCB11-related disorder.

What condition is associated with ABCB11 p.Arg52Gln (c.155G>A)?

ABCB11 p.Arg52Gln (c.155G>A) is associated with ABCB11-related disorder (ClinVar).

How common is ABCB11 p.Arg52Gln (c.155G>A) in the general population?

ABCB11 p.Arg52Gln (c.155G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ABCB11 p.Arg52Gln (c.155G>A)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg52Gln

c.155G>A · rs773884264 · VCV596195

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ABCB11-related disorder

Computational evidence

Protein change
AlphaMissense	0.1327	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.66	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 0.81
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00335% 54/1,612,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.129%	777
Middle Easterngrpmax	0.0165%	6,074
Remaining individualsnot grpmax-eligible	0.00481%	20,795
Admixed American	0.00335%	29,883
African / African-American	0.00134%	74,734
European (non-Finnish)	0.000763%	130,993

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg52Gln
Coding: c.155G>A
MANE Select: NM_003742
dbSNP: rs773884264
Type: single nucleotide variant
Location: chr2:169013506 (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 52: a turn

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCB11-related disorder

Similar variants

ABCB11 p.Arg52Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Arg52= Likely benign ★ same residue
ABCB11 c.611+1G>A Pathogenic ★★ same condition
ABCB11 c.909-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Arg1050Cys Pathogenic ★★ ⚠ same condition
ABCB11 p.Arg1057Ter Pathogenic ★★ same condition
ABCB11 p.Arg1235Ter Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Arg487His 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-arg52gln (accessed [today's date]).

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