Is DUSP3 p.His58Arg (c.173A>G) pathogenic?

DUSP3 p.His58Arg (c.173A>G) is classified Uncertain significance in DUSP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely pathogenic (0.8477); Absent from gnomAD v4.1.

How common is DUSP3 p.His58Arg (c.173A>G) in the general population?

DUSP3 p.His58Arg (c.173A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP3 p.His58Arg (c.173A>G)?

AlphaMissense predicts likely pathogenic (score 0.8477) — an in-silico prediction, not a clinical call.

DUSP3 p.His58Arg

c.173A>G · VCV4245580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8477	likely pathogenic
REVEL	0.919	moderately pathogenic-leaning
SaProt	LLR -11.64	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 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,312 bp · p 0.0071 · regional, not allelic
Overall
CADD	27.0	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

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: DUSP3
Protein: p.His58Arg
Coding: c.173A>G
MANE Select: NM_004090
Type: single nucleotide variant
Location: chr17:43774891 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 96.10 · 9 PDB
Residue 58: the tyrosine-protein phosphatase domain; a β-strand

Full DUSP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP3 p.Arg104Thr Uncertain significance ★ ⚠ same type
DUSP3 p.Arg119Gln Uncertain significance ★ ⚠ same type
DUSP3 p.Arg125Trp Uncertain significance ★ ⚠ same type
DUSP3 p.Arg158Cys Uncertain significance ★ ⚠ same type
DUSP3 p.Asn174Ser Uncertain significance ★ ⚠ same type
DUSP3 p.Asn74Ser Uncertain significance ★ ⚠ same type
DUSP3 p.Asp164Tyr Uncertain significance ★ ⚠ same type
DUSP3 p.Gln10Glu 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/dusp3-p-his58arg (accessed [today's date]).

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