Is DUSP22 p.Ile100Met (c.300C>G) pathogenic?

DUSP22 p.Ile100Met (c.300C>G) is classified Uncertain significance in DUSP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.2379); Absent from gnomAD v4.1.

How common is DUSP22 p.Ile100Met (c.300C>G) in the general population?

DUSP22 p.Ile100Met (c.300C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP22 p.Ile100Met (c.300C>G)?

AlphaMissense predicts likely benign (score 0.2379) — an in-silico prediction, not a clinical call.

DUSP22 p.Ile100Met

c.300C>G · VCV4245548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2379 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2379	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.9
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	2.611	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP22
Protein: p.Ile100Met
Coding: c.300C>G
MANE Select: NM_001286555
Type: single nucleotide variant
Location: chr6:348139 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB
Residue 100: 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-ile100met (accessed [today's date]).

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