Is DUSP22 p.His38Arg (c.113A>G) pathogenic?

DUSP22 p.His38Arg (c.113A>G) is classified Uncertain significance in DUSP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely pathogenic (0.9408); Very rare (popmax 0.00671%, eas).

How common is DUSP22 p.His38Arg (c.113A>G) in the general population?

DUSP22 p.His38Arg (c.113A>G) is very rare (popmax 0.00671%, eas) (gnomAD).

What do computational predictors say about DUSP22 p.His38Arg (c.113A>G)?

AlphaMissense predicts likely pathogenic (score 0.9408) — an in-silico prediction, not a clinical call.

DUSP22 p.His38Arg

c.113A>G · VCV3274061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9408	likely pathogenic
REVEL	0.327	indeterminate
SaProt	LLR -13.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	28.3	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 0.00671% East Asian · 3/44,742 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.00031% 5/1,612,744 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00671%	14,914
Remaining individualsnot grpmax-eligible	0.0016%	62,396
European (non-Finnish)	8.48e-05%	1,179,262

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.His38Arg
Coding: c.113A>G
MANE Select: NM_001286555
Type: single nucleotide variant
Location: chr6:311937 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 38: the tyrosine-protein phosphatase domain; a β-strand

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-his38arg (accessed [today's date]).

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