Is DUSP22 p.Val143Ile (c.427G>A) pathogenic?

DUSP22 p.Val143Ile (c.427G>A) is classified Likely benign in DUSP22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.1128); Rare (popmax 0.147%, nfe); Associated with DUSP22-related disorder.

What condition is associated with DUSP22 p.Val143Ile (c.427G>A)?

DUSP22 p.Val143Ile (c.427G>A) is associated with DUSP22-related disorder (ClinVar).

How common is DUSP22 p.Val143Ile (c.427G>A) in the general population?

DUSP22 p.Val143Ile (c.427G>A) is rare (popmax 0.147%, nfe) (gnomAD).

What do computational predictors say about DUSP22 p.Val143Ile (c.427G>A)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

DUSP22 p.Val143Ile

c.427G>A · rs147464089 · VCV3049760

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.147%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DUSP22-related disorder

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -9.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% European (non-Finnish) · 1,739/1,179,292 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.136% 2,201/1,613,302 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.459%	218
European (non-Finnish)grpmax	0.147%	678
Remaining individualsnot grpmax-eligible	0.107%	933
Admixed American	0.085%	1,177
Middle Eastern	0.0495%	2,020
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
South Asian	0.0242%	4,140
African / African-American	0.024%	4,172

Finnish 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.Val143Ile
Coding: c.427G>A
MANE Select: NM_001286555
dbSNP: rs147464089
Type: single nucleotide variant
Location: chr6:348266 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 143: the tyrosine-protein phosphatase domain; an α-helix

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-val143ile (accessed [today's date]).

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