Is ABCB11 p.Val95Ile (c.283G>A) pathogenic?

ABCB11 p.Val95Ile (c.283G>A) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-14). AlphaMissense: likely benign (0.0598); Ultra-rare (popmax 0.0317%, amr); Associated with ABCB11-related disorder.

What condition is associated with ABCB11 p.Val95Ile (c.283G>A)?

ABCB11 p.Val95Ile (c.283G>A) is associated with ABCB11-related disorder, familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Val95Ile (c.283G>A) in the general population?

ABCB11 p.Val95Ile (c.283G>A) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about ABCB11 p.Val95Ile (c.283G>A)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

ABCB11 p.Val95Ile

c.283G>A · rs201735739 · VCV1106992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCB11-related disorder

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -4.14	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 0.46	GERP -0.53, phastCons 0.001
Overall
CADD	1.056	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 0.0317% Admixed American · 19/59,980 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00248% 40/1,613,678 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,157
East Asian	0.00668%	14,959
South Asian	0.0022%	45,536
African / African-American	0.00134%	74,890
European (non-Finnish)	0.00127%	78,652

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.Val95Ile
Coding: c.283G>A
MANE Select: NM_003742
dbSNP: rs201735739
Type: single nucleotide variant
Location: chr2:169013378 (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

ABCB11-related disorder

Also linked: familial intrahepatic cholestasis

Similar variants

ABCB11 p.Val95Ala Uncertain significance ★ ⚠ same residue
ABCB11 p.Val95= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T 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-val95ile (accessed [today's date]).

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