Is ABCB5 p.Ala589Val (c.1766C>T) pathogenic?

ABCB5 p.Ala589Val (c.1766C>T) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1455); Absent from gnomAD v4.1.

How common is ABCB5 p.Ala589Val (c.1766C>T) in the general population?

ABCB5 p.Ala589Val (c.1766C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB5 p.Ala589Val (c.1766C>T)?

AlphaMissense predicts likely benign (score 0.1455) — an in-silico prediction, not a clinical call.

ABCB5 p.Ala589Val

c.1766C>T · VCV3292239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1455	likely benign
REVEL	0.718	pathogenic-leaning
SaProt	LLR -9.41	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	23.4	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: ABCB5
Protein: p.Ala589Val
Coding: c.1766C>T
MANE Select: NM_001163941
Type: single nucleotide variant
Location: chr7:20681563 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01
Residue 589: the abc transporter 1 domain

Full ABCB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB5 p.Ala350Thr Likely benign ★★ ⚠ same type
ABCB5 p.Val1209Ala Likely benign ★★ ⚠ same type
ABCB5 p.Ala1112Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala1154Gly Uncertain significance ★ ⚠ same type
ABCB5 p.Ala221Val Uncertain significance ★ ⚠ same type
ABCB5 p.Ala223Ser Uncertain significance ★ ⚠ same type
ABCB5 p.Ala327Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala501Glu Uncertain significance ★ ⚠ 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/abcb5-p-ala589val (accessed [today's date]).

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