Is ABCB4 p.Val192Ala (c.575T>C) pathogenic?

ABCB4 p.Val192Ala (c.575T>C) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: likely benign (0.149); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCB4 p.Val192Ala (c.575T>C)?

ABCB4 p.Val192Ala (c.575T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB4 p.Val192Ala (c.575T>C) in the general population?

ABCB4 p.Val192Ala (c.575T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB4 p.Val192Ala (c.575T>C)?

AlphaMissense predicts likely benign (score 0.149) — an in-silico prediction, not a clinical call.

ABCB4 p.Val192Ala

c.575T>C · VCV3863730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.149 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.149	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -10.61	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 31 kb · p 4.4e-11 · regional, not allelic
Overall
CADD	24.2	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: ABCB4
Protein: p.Val192Ala
Coding: c.575T>C
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87451756 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 192: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB4 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

ABCB4 p.Val192Phe Uncertain significance ★★ ⚠ same residue
ABCB4 p.Val192Ile Uncertain significance ★ ⚠ same residue
ABCB4 p.Val192Leu Uncertain significance ★ ⚠ same residue
ABCB4 p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala304Ser Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala333Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg159Gln Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg661His 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/abcb4-p-val192ala (accessed [today's date]).

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