Is DUSP22 p.His87Arg (c.260A>G) pathogenic?

DUSP22 p.His87Arg (c.260A>G) is classified Uncertain significance in DUSP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.9926); Very rare (popmax 0.000339%, nfe).

How common is DUSP22 p.His87Arg (c.260A>G) in the general population?

DUSP22 p.His87Arg (c.260A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DUSP22 p.His87Arg (c.260A>G)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

DUSP22 p.His87Arg

c.260A>G · rs1001711035 · VCV2464150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic · top 6% in DUSP22
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -15.22	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	29.2	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 0.000339% European (non-Finnish) · 4/1,180,002 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00254% 41/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Finnishnot grpmax-eligible	0.00156%	64,044
European (non-Finnish)grpmax	0.000339%	295,001

Ashkenazi Jewish 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.His87Arg
Coding: c.260A>G
MANE Select: NM_001286555
dbSNP: rs1001711035
Type: single nucleotide variant
Location: chr6:345925 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 87: 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-his87arg (accessed [today's date]).

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