Is ABCB11 p.Arg470Pro (c.1409G>C) pathogenic?

ABCB11 p.Arg470Pro (c.1409G>C) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.9841); Very rare (popmax 8.49e-05%, nfe).

How common is ABCB11 p.Arg470Pro (c.1409G>C) in the general population?

ABCB11 p.Arg470Pro (c.1409G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ABCB11 p.Arg470Pro (c.1409G>C)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg470Pro

c.1409G>C · VCV3896580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 2% in ABCB11
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -16.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.49e-05% European (non-Finnish) · 1/1,178,534 alleles

Overall 6.85e-05% 1/1,459,932 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.Arg470Pro
Coding: c.1409G>C
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168973740 (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 470: the abc transporter 1 domain

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

Similar variants

ABCB11 p.Arg470Gln Pathogenic/Likely pathogenic ★★ same residue
ABCB11 p.Arg470Ter Pathogenic ★★ same residue
ABCB11 p.Arg470Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Arg470= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same type
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-2A>C Likely pathogenic ★★ same type

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-arg470pro (accessed [today's date]).

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