Is DUSP28 p.Met89Ile (c.267G>A) pathogenic?

DUSP28 p.Met89Ile (c.267G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: ambiguous (0.4787); Ultra-rare (popmax 0.033%, afr).

How common is DUSP28 p.Met89Ile (c.267G>A) in the general population?

DUSP28 p.Met89Ile (c.267G>A) is ultra-rare (popmax 0.033%, afr) (gnomAD).

What do computational predictors say about DUSP28 p.Met89Ile (c.267G>A)?

AlphaMissense predicts ambiguous (score 0.4787) — an in-silico prediction, not a clinical call.

DUSP28 p.Met89Ile

c.267G>A · VCV3842925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4787	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -3.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.39	GERP -1, phastCons 0.99
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	15.36	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 0.033% African / African-American · 23/69,664 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0191%

Overall 0.00164% 25/1,524,542 alleles · ultra-rare exomes 13/1,372,486 · genomes 12/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.033%	3,029
Admixed American	0.00212%	47,104
Remaining individualsnot grpmax-eligible	0.00169%	59,118

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: DUSP28
Protein: p.Met89Ile
Coding: c.267G>A
MANE Select: NM_001370465
Type: single nucleotide variant
Location: chr2:240560951 (GRCh38)

Full DUSP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp28-p-met89ile (accessed [today's date]).

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