Is DUSP9 p.Pro18Gln (c.53C>A) pathogenic?

DUSP9 p.Pro18Gln (c.53C>A) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.0905); Ultra-rare (popmax 0.0128%, amr).

How common is DUSP9 p.Pro18Gln (c.53C>A) in the general population?

DUSP9 p.Pro18Gln (c.53C>A) is ultra-rare (popmax 0.0128%, amr) (gnomAD).

What do computational predictors say about DUSP9 p.Pro18Gln (c.53C>A)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

DUSP9 p.Pro18Gln

c.53C>A · VCV3274106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.92	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 1.9	GERP 1.1, phastCons 0.082
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	17.41	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 0.0128% Admixed American · 4/31,179 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.000404% 4/988,958 alleles · ultra-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.Pro18Gln
Coding: c.53C>A
MANE Select: NM_001318503
Type: single nucleotide variant
Location: chrX:153648006 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 18: the rhodanese domain

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

Similar variants

DUSP9 p.Pro18Leu 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
DUSP9 p.Ala45Thr 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-pro18gln (accessed [today's date]).

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