Is ABCB11 p.Cys161Arg (c.481T>C) pathogenic?

ABCB11 p.Cys161Arg (c.481T>C) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: ambiguous (0.424); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Cys161Arg (c.481T>C)?

ABCB11 p.Cys161Arg (c.481T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Cys161Arg (c.481T>C) in the general population?

ABCB11 p.Cys161Arg (c.481T>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ABCB11 p.Cys161Arg (c.481T>C)?

AlphaMissense predicts ambiguous (score 0.424) — an in-silico prediction, not a clinical call.

ABCB11 p.Cys161Arg

c.481T>C · rs1694683796 · VCV2285428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.424	ambiguous
REVEL	0.196	benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 0.72, phastCons 1
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,812 alleles

Overall 6.86e-05% 1/1,456,932 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.Cys161Arg
Coding: c.481T>C
MANE Select: NM_003742
dbSNP: rs1694683796
Type: single nucleotide variant
Location: chr2:168995479 (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 161: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB11 p.Cys161Ter Pathogenic ★★ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Asp1236Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Cys1117Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Glu395Asp Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu581Val Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu644Pro Uncertain significance ★★ ⚠ 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-cys161arg (accessed [today's date]).

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