Is DUSP4 p.Arg313His (c.938G>A) pathogenic?

DUSP4 p.Arg313His (c.938G>A) is classified Uncertain significance in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely pathogenic (0.7143); Very rare (popmax 0.00223%, eas).

How common is DUSP4 p.Arg313His (c.938G>A) in the general population?

DUSP4 p.Arg313His (c.938G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DUSP4 p.Arg313His (c.938G>A)?

AlphaMissense predicts likely pathogenic (score 0.7143) — an in-silico prediction, not a clinical call.

DUSP4 p.Arg313His

c.938G>A · rs773054971 · VCV2285488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7143	likely pathogenic
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -12.48	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 304 bp · p 0.00077 · regional, not allelic
Overall
CADD	29.5	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000137% 2/1,461,330 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: DUSP4
Protein: p.Arg313His
Coding: c.938G>A
MANE Select: NM_001394
dbSNP: rs773054971
Type: single nucleotide variant
Location: chr8:29337273 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.78 · 1 PDB
Residue 313: the tyrosine-protein phosphatase domain

Full DUSP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP4 p.Ala163Gly Uncertain significance ★ ⚠ same type
DUSP4 p.Ala166Thr Uncertain significance ★ ⚠ same type
DUSP4 p.Ala212Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Ala341Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Trp Uncertain significance ★ ⚠ same type
DUSP4 p.Arg273His Uncertain significance ★ ⚠ same type
DUSP4 p.Asp180Tyr 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/dusp4-p-arg313his (accessed [today's date]).

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