Is DUSP22 p.Val129Leu (c.385G>T) pathogenic?

DUSP22 p.Val129Leu (c.385G>T) is classified Likely benign in DUSP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.1496); Very rare (popmax 0.008%, afr).

How common is DUSP22 p.Val129Leu (c.385G>T) in the general population?

DUSP22 p.Val129Leu (c.385G>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about DUSP22 p.Val129Leu (c.385G>T)?

AlphaMissense predicts likely benign (score 0.1496) — an in-silico prediction, not a clinical call.

DUSP22 p.Val129Leu

c.385G>T · VCV4662557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1496 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1496	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -4.17	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 0.68	GERP -1.2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	13.93	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 0.008% African / African-American · 6/74,964 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000372% 6/1,614,194 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.Val129Leu
Coding: c.385G>T
MANE Select: NM_001286555
Type: single nucleotide variant
Location: chr6:348224 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 129: 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 p.Val129Met Uncertain significance ★ ⚠ same residue
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

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-val129leu (accessed [today's date]).

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