Is ABCB11 p.Leu80Pro (c.239T>C) pathogenic?

ABCB11 p.Leu80Pro (c.239T>C) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-04). AlphaMissense: likely pathogenic (0.9372); Absent from gnomAD v4.1.

How common is ABCB11 p.Leu80Pro (c.239T>C) in the general population?

ABCB11 p.Leu80Pro (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB11 p.Leu80Pro (c.239T>C)?

AlphaMissense predicts likely pathogenic (score 0.9372) — an in-silico prediction, not a clinical call.

ABCB11 p.Leu80Pro

c.239T>C · rs886042487 · VCV282811

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9372 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9372	likely pathogenic · top 7% in ABCB11
REVEL	0.662	pathogenic-leaning
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 0.99
Overall
CADD	25.2	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.Leu80Pro
Coding: c.239T>C
MANE Select: NM_003742
dbSNP: rs886042487
Type: single nucleotide variant
Location: chr2:169013422 (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 80: the abc transmembrane type-1 1 domain; an α-helix

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

Similar variants

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
ABCB11 c.150+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.150+3A>C 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-leu80pro (accessed [today's date]).

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