Is DUSP9 p.Arg342Leu (c.1025G>T) pathogenic?

DUSP9 p.Arg342Leu (c.1025G>T) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-30). AlphaMissense: likely benign (0.2982); Very rare (popmax 0.00701%, sas).

How common is DUSP9 p.Arg342Leu (c.1025G>T) in the general population?

DUSP9 p.Arg342Leu (c.1025G>T) is very rare (popmax 0.00701%, sas) (gnomAD).

What do computational predictors say about DUSP9 p.Arg342Leu (c.1025G>T)?

AlphaMissense predicts likely benign (score 0.2982) — an in-silico prediction, not a clinical call.

DUSP9 p.Arg342Leu

c.1025G>T · rs782339585 · VCV2252970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00701%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2982	likely benign
REVEL	0.546	indeterminate
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.00701% South Asian · 4/57,060 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000364% 4/1,098,031 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: DUSP9
Protein: p.Arg342Leu
Coding: c.1025G>T
MANE Select: NM_001318503
dbSNP: rs782339585
Type: single nucleotide variant
Location: chrX:153650175 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 342: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP9 p.Arg342Cys Uncertain significance ★ ⚠ same residue
DUSP9 p.Arg342His Uncertain significance ★ ⚠ same residue
DUSP9 p.Ala151Val Benign ★★ same type
DUSP9 p.Ala174= Benign ★★ same type
DUSP9 p.Pro158= Benign ★★ same type
DUSP9 p.Ala174Val Uncertain significance ★ ⚠ same type
DUSP9 p.Ala226Ser Uncertain significance ★ ⚠ same type
DUSP9 p.Ala362Val 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/dusp9-p-arg342leu (accessed [today's date]).

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