Is DUSP9 p.Ser351Trp (c.1052C>G) pathogenic?

DUSP9 p.Ser351Trp (c.1052C>G) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.00268%, nfe).

How common is DUSP9 p.Ser351Trp (c.1052C>G) in the general population?

DUSP9 p.Ser351Trp (c.1052C>G) is very rare (popmax 0.00268%, nfe) (gnomAD).

What do computational predictors say about DUSP9 p.Ser351Trp (c.1052C>G)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

DUSP9 p.Ser351Trp

c.1052C>G · VCV3274104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -2.6
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% European (non-Finnish) · 24/895,354 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00152%

Overall 0.00198% 24/1,210,760 alleles · very rare exomes 23/1,097,823 · genomes 1/112,937 · joint denominator

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.Ser351Trp
Coding: c.1052C>G
MANE Select: NM_001318503
Type: single nucleotide variant
Location: chrX:153650202 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 351: the 'disordered' region; a modified residue (phosphoserine)

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-ser351trp (accessed [today's date]).

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