Is DUSP5 p.Cys28Trp (c.84C>G) pathogenic?

DUSP5 p.Cys28Trp (c.84C>G) is classified Uncertain significance in DUSP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely pathogenic (0.9974); No allele count reported in gnomAD v4.1 (AN 1,509,456).

How common is DUSP5 p.Cys28Trp (c.84C>G) in the general population?

DUSP5 p.Cys28Trp (c.84C>G) is no allele count reported in gnomAD v4.1 (AN 1,509,456) (gnomAD).

What do computational predictors say about DUSP5 p.Cys28Trp (c.84C>G)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

DUSP5 p.Cys28Trp

c.84C>G · VCV3505912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,509,456)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic · top 3% in DUSP5
REVEL	0.365	indeterminate
SaProt	LLR -14.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 8,933 bp · p 6.1e-05 · 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

No allele count reported in gnomAD v4.1 (AN 1,509,456). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DUSP5
Protein: p.Cys28Trp
Coding: c.84C>G
MANE Select: NM_004419
Type: single nucleotide variant
Location: chr10:110498205 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.76 · 1 PDB
Residue 28: the rhodanese domain

Full DUSP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP5 p.Asp291Asn Uncertain significance ★★ ⚠ same type
DUSP5 p.Ala55Ser Benign ★★ same type
DUSP5 p.Ala104Val Uncertain significance ★ ⚠ same type
DUSP5 p.Ala59Pro Uncertain significance ★ ⚠ same type
DUSP5 p.Arg121Leu Uncertain significance ★ ⚠ same type
DUSP5 p.Arg16Ser Uncertain significance ★ ⚠ same type
DUSP5 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP5 p.Arg269Cys 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/dusp5-p-cys28trp (accessed [today's date]).

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