Is ABCB11 p.Ala151Val (c.452C>T) pathogenic?

ABCB11 p.Ala151Val (c.452C>T) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0737); Very rare (popmax 0.00273%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Ala151Val (c.452C>T)?

ABCB11 p.Ala151Val (c.452C>T) is associated with Inborn genetic diseases, progressive familial intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Ala151Val (c.452C>T) in the general population?

ABCB11 p.Ala151Val (c.452C>T) is very rare (popmax 0.00273%, afr) (gnomAD).

What do computational predictors say about ABCB11 p.Ala151Val (c.452C>T)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

ABCB11 p.Ala151Val

c.452C>T · VCV4068321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -2.3
Overall
CADD	7.875	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00273% African / African-American · 2/73,342 alleles

Filtering AF 0.000453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.000319% 5/1,565,914 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00273%	36,671
East Asian	0.00233%	42,920
European (non-Finnish)	0.000174%	576,356

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.Ala151Val
Coding: c.452C>T
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168996660 (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 151: 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

Also linked: progressive familial intrahepatic cholestasis type 2

Similar variants

ABCB11 p.Ala151Thr Uncertain significance ★★ ⚠ same residue
ABCB11 p.Ala151= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.150+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>C 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-ala151val (accessed [today's date]).

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