Is DUSP3 p.Arg158Cys (c.472C>T) pathogenic?

DUSP3 p.Arg158Cys (c.472C>T) is classified Uncertain significance in DUSP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely pathogenic (0.9737); Very rare (popmax 0.00533%, afr).

How common is DUSP3 p.Arg158Cys (c.472C>T) in the general population?

DUSP3 p.Arg158Cys (c.472C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about DUSP3 p.Arg158Cys (c.472C>T)?

AlphaMissense predicts likely pathogenic (score 0.9737) — an in-silico prediction, not a clinical call.

DUSP3 p.Arg158Cys

c.472C>T · VCV3842934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9737	likely pathogenic
REVEL	0.723	pathogenic-leaning
SaProt	LLR -14.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,312 bp · p 0.0071 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00533% African / African-American · 4/75,028 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00186% 30/1,613,814 alleles · very rare exomes 25/1,461,508 · genomes 5/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,757
European (non-Finnish)	0.0022%	45,383

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: DUSP3
Protein: p.Arg158Cys
Coding: c.472C>T
MANE Select: NM_004090
Type: single nucleotide variant
Location: chr17:43769695 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 96.10 · 9 PDB
Residue 158: the tyrosine-protein phosphatase domain

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.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
DUSP3 p.Glu103Lys 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-arg158cys (accessed [today's date]).

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