Is DUSP28 p.Phe130Ser (c.389T>C) pathogenic?

DUSP28 p.Phe130Ser (c.389T>C) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely pathogenic (0.9713); Ultra-rare (popmax 0.0241%, mid).

How common is DUSP28 p.Phe130Ser (c.389T>C) in the general population?

DUSP28 p.Phe130Ser (c.389T>C) is ultra-rare (popmax 0.0241%, mid) (gnomAD).

What do computational predictors say about DUSP28 p.Phe130Ser (c.389T>C)?

AlphaMissense predicts likely pathogenic (score 0.9713) — an in-silico prediction, not a clinical call.

DUSP28 p.Phe130Ser

c.389T>C · VCV4015424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9713	likely pathogenic · top 8% in DUSP28
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -12.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	28.5	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 0.0241% Middle Eastern · 1/4,148 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00075%

Overall 0.00188% 28/1,486,300 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0241%	4,148
Remaining individualsnot grpmax-eligible	0.0122%	8,192
South Asian	0.00393%	25,419
European (non-Finnish)	0.00151%	66,354

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.Phe130Ser
Coding: c.389T>C
MANE Select: NM_001370465
Type: single nucleotide variant
Location: chr2:240561073 (GRCh38)
Gene constraint: LOEUF 1.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.88 · 2 PDB
Residue 130: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

DUSP28 p.Ala129Pro Uncertain significance ★ ⚠ same type
DUSP28 p.Ala136Ser Uncertain significance ★ ⚠ same type
DUSP28 p.Cys114Tyr Uncertain significance ★ ⚠ same type
DUSP28 p.Gln131Arg Uncertain significance ★ ⚠ same type
DUSP28 p.Glu154Gln Uncertain significance ★ ⚠ same type
DUSP28 p.Glu155Ala Uncertain significance ★ ⚠ same type
DUSP28 p.Leu150Phe Uncertain significance ★ ⚠ same type
DUSP28 p.Leu163Pro 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/dusp28-p-phe130ser (accessed [today's date]).

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