Is ABCB11 p.Arg415Pro (c.1244G>C) pathogenic?

ABCB11 p.Arg415Pro (c.1244G>C) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-17). AlphaMissense: ambiguous (0.4413); Very rare (popmax 0.00267%, afr).

How common is ABCB11 p.Arg415Pro (c.1244G>C) in the general population?

ABCB11 p.Arg415Pro (c.1244G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ABCB11 p.Arg415Pro (c.1244G>C)?

AlphaMissense predicts ambiguous (score 0.4413) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg415Pro

c.1244G>C · rs371656014 · VCV597261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.4413	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -8.41	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.35, phastCons 1
Overall
CADD	24.0	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

Grpmax group 0.00267% African / African-American · 2/74,836 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00132% 2/152,030 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.Arg415Pro
Coding: c.1244G>C
MANE Select: NM_003742
dbSNP: rs371656014
Type: single nucleotide variant
Location: chr2:168976641 (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 415: a UniProt-annotated variant site (in)

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

Similar variants

ABCB11 p.Arg415Ter Pathogenic ★★ same residue
ABCB11 p.Arg415Gln Uncertain significance ★★ ⚠ 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
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.150+1G>A Pathogenic/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-arg415pro (accessed [today's date]).

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