Is DUSP28 p.Val49Asp (c.146T>A) pathogenic?

DUSP28 p.Val49Asp (c.146T>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.9963); Ultra-rare (popmax 0.0247%, mid).

How common is DUSP28 p.Val49Asp (c.146T>A) in the general population?

DUSP28 p.Val49Asp (c.146T>A) is ultra-rare (popmax 0.0247%, mid) (gnomAD).

What do computational predictors say about DUSP28 p.Val49Asp (c.146T>A)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

DUSP28 p.Val49Asp

c.146T>A · VCV4662563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic
REVEL	0.763	pathogenic-leaning
SaProt	LLR -18.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	31.0	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 0.0247% Middle Eastern · 1/4,046 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.00198% 28/1,417,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0247%	4,046
South Asian	0.00298%	33,515
European (non-Finnish)	0.00219%	45,595
Remaining individualsnot grpmax-eligible	0.00184%	54,334

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.Val49Asp
Coding: c.146T>A
MANE Select: NM_001282771 · reported on NM_001370465
Type: single nucleotide variant
Location: chr2:240560830 (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-val49asp (accessed [today's date]).

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