Is DUSP2 p.Val89Met (c.265G>A) pathogenic?

DUSP2 p.Val89Met (c.265G>A) is classified Uncertain significance in DUSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely pathogenic (0.7822); Very rare (popmax 0.00018%, nfe).

How common is DUSP2 p.Val89Met (c.265G>A) in the general population?

DUSP2 p.Val89Met (c.265G>A) is very rare (popmax 0.00018%, nfe) (gnomAD).

What do computational predictors say about DUSP2 p.Val89Met (c.265G>A)?

AlphaMissense predicts likely pathogenic (score 0.7822) — an in-silico prediction, not a clinical call.

DUSP2 p.Val89Met

c.265G>A · rs1405404364 · VCV2535274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00018%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7822	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	LLR -13.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.42, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,528 bp · p 0.41 · regional, not allelic
Overall
CADD	24.5	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 0.00018% European (non-Finnish) · 2/1,113,754 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000153% 2/1,305,068 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: DUSP2
Protein: p.Val89Met
Coding: c.265G>A
MANE Select: NM_004418
dbSNP: rs1405404364
Type: single nucleotide variant
Location: chr2:96145090 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.59 · 1 PDB
Residue 89: the rhodanese domain

Full DUSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP2 p.Ala107Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala265Pro Uncertain significance ★ same type
DUSP2 p.Ala265Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala45Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala65Gly Uncertain significance ★ ⚠ same type
DUSP2 p.Arg263Cys Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26His Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26Ser 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/dusp2-p-val89met (accessed [today's date]).

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