Is DUSP22 p.Pro195Leu (c.584C>T) pathogenic?

DUSP22 p.Pro195Leu (c.584C>T) is classified Likely benign in DUSP22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-19). Rare (popmax 0.57%, nfe); Associated with DUSP22-related disorder.

What condition is associated with DUSP22 p.Pro195Leu (c.584C>T)?

DUSP22 p.Pro195Leu (c.584C>T) is associated with DUSP22-related disorder (ClinVar).

How common is DUSP22 p.Pro195Leu (c.584C>T) in the general population?

DUSP22 p.Pro195Leu (c.584C>T) is rare (popmax 0.57%, nfe) (gnomAD).

DUSP22 p.Pro195Leu

c.584C>T · rs201957282 · VCV3042277

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.57%, nfe)

Conditions

DUSP22-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 0.52
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.57% European (non-Finnish) · 6,710/1,177,336 alleles

Filtering AF 0.558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.554%

Overall 0.473% 7,610/1,610,170 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.22%	82
European (non-Finnish)grpmax	0.57%	175
Admixed American	0.563%	177
Remaining individualsnot grpmax-eligible	0.385%	260
Middle Eastern	0.248%	403
Ashkenazi Jewishnot grpmax-eligible	0.23%	434
Finnishnot grpmax-eligible	0.141%	709
African / African-American	0.0973%	1,028
South Asian	0.0737%	1,357
East Asian	0.00223%	44,780

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DUSP22
Protein: p.Pro195Leu
Coding: c.584C>T
MANE Select: NM_001286555
dbSNP: rs201957282
Type: single nucleotide variant
Location: chr6:348917 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB

Full DUSP22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DUSP22-related disorder

Similar variants

DUSP22 c.189-4C>T Likely benign same condition
DUSP22 c.-5C>T Likely benign same condition
DUSP22 c.*1871C>G Likely benign same condition
DUSP22 c.*1878G>A Benign same condition
DUSP22 c.*2G>A Likely benign same condition
DUSP22 c.*8G>A Likely benign same condition
DUSP22 p.Ala23= Likely benign same condition
DUSP22 p.Ala56= Likely benign same condition

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/dusp22-p-pro195leu (accessed [today's date]).

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