Is DUSP9 p.Arg349Cys (c.1045C>T) pathogenic?

DUSP9 p.Arg349Cys (c.1045C>T) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0973); Very rare (popmax 0.0089%, eas).

How common is DUSP9 p.Arg349Cys (c.1045C>T) in the general population?

DUSP9 p.Arg349Cys (c.1045C>T) is very rare (popmax 0.0089%, eas) (gnomAD).

What do computational predictors say about DUSP9 p.Arg349Cys (c.1045C>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

DUSP9 p.Arg349Cys

c.1045C>T · rs147422194 · VCV2278060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.064	GERP -3.1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	14.96	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 0.0089% East Asian · 3/33,725 alleles

Filtering AF 0.00236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.000661% 8/1,210,875 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0089%	11,242
Admixed American	0.00217%	46,021
Remaining individualsnot grpmax-eligible	0.0021%	47,642
South Asian	0.00176%	56,969
European (non-Finnish)	0.000223%	447,668

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.Arg349Cys
Coding: c.1045C>T
MANE Select: NM_001318503
dbSNP: rs147422194
Type: single nucleotide variant
Location: chrX:153650195 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 349: the 'disordered' region

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

Similar variants

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
DUSP9 p.Ala45Thr Uncertain significance ★ ⚠ same type
DUSP9 p.Ala48Thr 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-arg349cys (accessed [today's date]).

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