Is DUSP28 p.Cys114Tyr (c.341G>A) pathogenic?

DUSP28 p.Cys114Tyr (c.341G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.9922); Ultra-rare (popmax 0.0143%, eas).

How common is DUSP28 p.Cys114Tyr (c.341G>A) in the general population?

DUSP28 p.Cys114Tyr (c.341G>A) is ultra-rare (popmax 0.0143%, eas) (gnomAD).

What do computational predictors say about DUSP28 p.Cys114Tyr (c.341G>A)?

AlphaMissense predicts likely pathogenic (score 0.9922) — an in-silico prediction, not a clinical call.

DUSP28 p.Cys114Tyr

c.341G>A · rs757425889 · VCV2613809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9922	likely pathogenic · top 2% in DUSP28
REVEL	0.607	indeterminate
SaProt	LLR -14.44	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	29.9	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 0.0143% East Asian · 6/41,826 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.000651% 10/1,536,506 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0143%	6,971
Finnishnot grpmax-eligible	0.00223%	44,768
Admixed American	0.00205%	48,790
Remaining individualsnot grpmax-eligible	0.00168%	59,482
European (non-Finnish)	8.67e-05%	1,153,086

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.Cys114Tyr
Coding: c.341G>A
MANE Select: NM_001370465
dbSNP: rs757425889
Type: single nucleotide variant
Location: chr2:240561025 (GRCh38)
Gene constraint: LOEUF 1.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.88 · 2 PDB
Residue 114: 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.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
DUSP28 p.Leu172Ser 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-cys114tyr (accessed [today's date]).

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