Is DUSP22 p.Gly130Arg (c.388G>C) pathogenic?

DUSP22 p.Gly130Arg (c.388G>C) is classified Uncertain significance in DUSP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.9888); Very rare (popmax 0.00223%, eas).

How common is DUSP22 p.Gly130Arg (c.388G>C) in the general population?

DUSP22 p.Gly130Arg (c.388G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DUSP22 p.Gly130Arg (c.388G>C)?

AlphaMissense predicts likely pathogenic (score 0.9888) — an in-silico prediction, not a clinical call.

DUSP22 p.Gly130Arg

c.388G>C · VCV4245547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9888	likely pathogenic · top 10% in DUSP22
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -14.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,892 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very 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: DUSP22
Protein: p.Gly130Arg
Coding: c.388G>C
MANE Select: NM_001286555
Type: single nucleotide variant
Location: chr6:348227 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 130: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

DUSP22 c.*1874C>G Uncertain significance ★ ⚠ same type
DUSP22 c.*1877C>T Uncertain significance ★ ⚠ same type
DUSP22 c.*1891T>C Uncertain significance ★ ⚠ same type
DUSP22 c.*1897G>A Uncertain significance ★ ⚠ same type
DUSP22 c.*1898C>A Uncertain significance ★ ⚠ same type
DUSP22 c.*1898C>T Uncertain significance ★ ⚠ same type
DUSP22 c.*1903C>T Uncertain significance ★ ⚠ same type
DUSP22 c.*1913T>A 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/dusp22-p-gly130arg (accessed [today's date]).

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