Is ABCB11 p.Arg487Pro (c.1460G>C) pathogenic?

ABCB11 p.Arg487Pro (c.1460G>C) is classified Pathogenic/Likely pathogenic in ABCB11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-14). AlphaMissense: likely pathogenic (0.9135); Absent from gnomAD v4.1; Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Arg487Pro (c.1460G>C)?

ABCB11 p.Arg487Pro (c.1460G>C) is associated with progressive familial intrahepatic cholestasis type 2, progressive familial intrahepatic cholestasis type 1, familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Arg487Pro (c.1460G>C) in the general population?

ABCB11 p.Arg487Pro (c.1460G>C) is absent from gnomAD v4.1 (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.Arg487Pro (c.1460G>C)?

AlphaMissense predicts likely pathogenic (score 0.9135) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg487Pro

c.1460G>C · rs188824058 · VCV1070887

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive familial intrahepatic cholestasis type 2

Computational evidence

Protein change
AlphaMissense	0.9135	likely pathogenic ✓ concordant with ClinVar · top 9% in ABCB11
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -12.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	33.0	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.Arg487Pro
Coding: c.1460G>C
MANE Select: NM_003742
dbSNP: rs188824058
Type: single nucleotide variant
Location: chr2:168972025 (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 487: the abc transporter 1 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

Also linked: progressive familial intrahepatic cholestasis type 1 familial intrahepatic cholestasis

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB11 p.Arg487Cys Likely pathogenic ★★ ⚠ same residue
ABCB11 p.Arg487His Pathogenic/Likely pathogenic ★★ ⚠ same residue
ABCB11 p.Arg487Leu Conflicting classifications of pathogenicity ★ ⚠ 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.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T 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-arg487pro (accessed [today's date]).

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