Is DUSP9 p.Pro158= (c.474C>T) pathogenic?

DUSP9 p.Pro158= (c.474C>T) is classified Benign in DUSP9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-14). Common (popmax 6.63%, afr) — too common for a highly-penetrant pathogenic allele.

DUSP9 p.Pro158=

Q: How common is DUSP9 p.Pro158= (c.474C>T) in the general population?

DUSP9 p.Pro158= (c.474C>T) is common (popmax 6.63%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.474C>T · rs73633708 · VCV780742

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.63%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.078	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -3.4
Overall
CADD	0.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.63% African / African-American · 3,799/57,318 alleles

Filtering AF 6.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.38%

Overall 0.354% 4,281/1,209,257 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.63%	15
Remaining individualsnot grpmax-eligible	0.429%	233
Middle Eastern	0.38%	263
Admixed American	0.377%	265
South Asian	0.0123%	8,121
European (non-Finnish)	0.00905%	11,052
East Asian	0.00296%	33,739

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.Pro158=
Coding: c.474C>T
MANE Select: NM_001318503
dbSNP: rs73633708
Type: single nucleotide variant
Location: chrX:153649332 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB

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.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
DUSP9 p.Arg145His 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-pro158 (accessed [today's date]).

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