Is DUSP28 p.Met132Ile (c.396G>A) pathogenic?

DUSP28 p.Met132Ile (c.396G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: ambiguous (0.4052); Absent from gnomAD v4.1.

How common is DUSP28 p.Met132Ile (c.396G>A) in the general population?

DUSP28 p.Met132Ile (c.396G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP28 p.Met132Ile (c.396G>A)?

AlphaMissense predicts ambiguous (score 0.4052) — an in-silico prediction, not a clinical call.

DUSP28 p.Met132Ile

c.396G>A · VCV4015429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4052 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4052	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -2.4
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	0.306	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: DUSP28
Protein: p.Met132Ile
Coding: c.396G>A
MANE Select: NM_001370465
Type: single nucleotide variant
Location: chr2:240561332 (GRCh38)
Gene constraint: LOEUF 1.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.88 · 2 PDB
Residue 132: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

DUSP28 p.Ala129Pro Uncertain significance ★ ⚠ same type
DUSP28 p.Ala136Ser Uncertain significance ★ ⚠ same type
DUSP28 p.Cys114Tyr Uncertain significance ★ ⚠ same type
DUSP28 p.Gln131Arg Uncertain significance ★ ⚠ same type
DUSP28 p.Glu154Gln Uncertain significance ★ ⚠ same type
DUSP28 p.Glu155Ala Uncertain significance ★ ⚠ same type
DUSP28 p.Leu150Phe Uncertain significance ★ ⚠ same type
DUSP28 p.Leu163Pro 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/dusp28-p-met132ile (accessed [today's date]).

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