Is ABCB11 p.Arg201Ser (c.603A>T) pathogenic?

ABCB11 p.Arg201Ser (c.603A>T) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: ambiguous (0.5415); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Arg201Ser (c.603A>T)?

ABCB11 p.Arg201Ser (c.603A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Arg201Ser (c.603A>T) in the general population?

ABCB11 p.Arg201Ser (c.603A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB11 p.Arg201Ser (c.603A>T)?

AlphaMissense predicts ambiguous (score 0.5415) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg201Ser

c.603A>T · rs1558915941 · VCV3120748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5415 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5415	ambiguous
REVEL	0.832	moderately pathogenic-leaning
SaProt	LLR -12.75	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP 0.76, phastCons 1
Overall
CADD	23.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB11
Protein: p.Arg201Ser
Coding: c.603A>T
MANE Select: NM_003742
dbSNP: rs1558915941
Type: single nucleotide variant
Location: chr2:168995357 (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 201: 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.Arg201= Likely benign ★ 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-arg201ser (accessed [today's date]).

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