Is DUSP28 p.Met119Lys (c.356T>A) pathogenic?

DUSP28 p.Met119Lys (c.356T>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.9664); Very rare (popmax 0.00366%, sas).

How common is DUSP28 p.Met119Lys (c.356T>A) in the general population?

DUSP28 p.Met119Lys (c.356T>A) is very rare (popmax 0.00366%, sas) (gnomAD).

What do computational predictors say about DUSP28 p.Met119Lys (c.356T>A)?

AlphaMissense predicts likely pathogenic (score 0.9664) — an in-silico prediction, not a clinical call.

DUSP28 p.Met119Lys

c.356T>A · rs1032543680 · VCV2481177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00366%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9664	likely pathogenic
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -13.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	26.4	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 0.00366% South Asian · 3/81,990 alleles

Filtering AF 0.000972% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000469%

Overall 0.000459% 7/1,524,592 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00366%	27,330
European (non-Finnish)	0.000349%	286,550

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: DUSP28
Protein: p.Met119Lys
Coding: c.356T>A
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs1032543680
Type: single nucleotide variant
Location: chr2:240561040 (GRCh38)

Full DUSP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp28-p-met119lys (accessed [today's date]).

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