Is ABCB11 p.Ile160Val (c.478A>G) pathogenic?

ABCB11 p.Ile160Val (c.478A>G) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-09). AlphaMissense: likely benign (0.1154); Very rare (popmax 0.00674%, amr).

How common is ABCB11 p.Ile160Val (c.478A>G) in the general population?

ABCB11 p.Ile160Val (c.478A>G) is very rare (popmax 0.00674%, amr) (gnomAD).

What do computational predictors say about ABCB11 p.Ile160Val (c.478A>G)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

ABCB11 p.Ile160Val

c.478A>G · rs774354809 · VCV594224

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00674%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP -1.7, phastCons 1
Overall
CADD	20.4	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 0.00674% Admixed American · 4/59,310 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00124% 20/1,609,178 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00674%	14,827
Remaining individualsnot grpmax-eligible	0.00643%	15,563
European (non-Finnish)	0.00102%	98,156

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.Ile160Val
Coding: c.478A>G
MANE Select: NM_003742
dbSNP: rs774354809
Type: single nucleotide variant
Location: chr2:168995482 (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 160: an α-helix; the abc transmembrane type-1 1 domain

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

Similar variants

ABCB11 p.Ile160Leu 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
ABCB11 c.150+2T>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-ile160val (accessed [today's date]).

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