Is ABCB11 p.Val95Ala (c.284T>C) pathogenic?

ABCB11 p.Val95Ala (c.284T>C) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.082); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Val95Ala (c.284T>C)?

ABCB11 p.Val95Ala (c.284T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Val95Ala (c.284T>C) in the general population?

ABCB11 p.Val95Ala (c.284T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABCB11 p.Val95Ala (c.284T>C)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

ABCB11 p.Val95Ala

c.284T>C · rs745952466 · VCV2492020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -3.81	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 -3.9
Overall
CADD	0.287	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 0.00223% East Asian · 1/44,874 alleles

Overall 6.84e-05% 1/1,461,548 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.Val95Ala
Coding: c.284T>C
MANE Select: NM_003742
dbSNP: rs745952466
Type: single nucleotide variant
Location: chr2:169013377 (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 95: the abc transmembrane type-1 1 domain; an α-helix

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

Similar variants

ABCB11 p.Val95Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Val95= Likely benign ★ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Asp1236Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Cys1117Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Glu395Asp Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu581Val Uncertain significance ★★ ⚠ 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-val95ala (accessed [today's date]).

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