Is DUSP1 p.Cys210Ser (c.628T>A) pathogenic?

DUSP1 p.Cys210Ser (c.628T>A) is classified Uncertain significance in DUSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely pathogenic (0.9913); Absent from gnomAD v4.1.

How common is DUSP1 p.Cys210Ser (c.628T>A) in the general population?

DUSP1 p.Cys210Ser (c.628T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP1 p.Cys210Ser (c.628T>A)?

AlphaMissense predicts likely pathogenic (score 0.9913) — an in-silico prediction, not a clinical call.

DUSP1 p.Cys210Ser

c.628T>A · VCV4015355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9913 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9913	likely pathogenic
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,309 bp · p 0.037 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP1
Protein: p.Cys210Ser
Coding: c.628T>A
MANE Select: NM_004417
Type: single nucleotide variant
Location: chr5:172769680 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 4 PDB
Residue 210: the tyrosine-protein phosphatase domain

Full DUSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP1 p.Ala103Val Uncertain significance ★ ⚠ same type
DUSP1 p.Ala113Gly Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala202Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala59Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala69Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala92Asp 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/dusp1-p-cys210ser (accessed [today's date]).

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