Is ABCB5 p.Trp128Arg (c.382T>C) pathogenic?

ABCB5 p.Trp128Arg (c.382T>C) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-08). AlphaMissense: likely pathogenic (0.9533); Very rare (popmax 0.000509%, nfe).

How common is ABCB5 p.Trp128Arg (c.382T>C) in the general population?

ABCB5 p.Trp128Arg (c.382T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about ABCB5 p.Trp128Arg (c.382T>C)?

AlphaMissense predicts likely pathogenic (score 0.9533) — an in-silico prediction, not a clinical call.

ABCB5 p.Trp128Arg

c.382T>C · rs770339087 · VCV2259380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9533	likely pathogenic · top 1% in ABCB5
REVEL	0.537	indeterminate
SaProt	LLR -13.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000509% European (non-Finnish) · 6/1,179,802 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,678 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: ABCB5
Protein: p.Trp128Arg
Coding: c.382T>C
MANE Select: NM_001163941
dbSNP: rs770339087
Type: single nucleotide variant
Location: chr7:20643251 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01
Residue 128: the abc transmembrane type-1 1 domain

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

Similar variants

ABCB5 p.Trp128Cys Uncertain significance ★ ⚠ same residue
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

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-trp128arg (accessed [today's date]).

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