Is DUSP4 p.Val372Ala (c.1115T>C) pathogenic?

DUSP4 p.Val372Ala (c.1115T>C) is classified Uncertain significance in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1669); Absent from gnomAD v4.1.

How common is DUSP4 p.Val372Ala (c.1115T>C) in the general population?

DUSP4 p.Val372Ala (c.1115T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP4 p.Val372Ala (c.1115T>C)?

AlphaMissense predicts likely benign (score 0.1669) — an in-silico prediction, not a clinical call.

DUSP4 p.Val372Ala

c.1115T>C · VCV4662583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1669 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1669	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 304 bp · p 0.00077 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: DUSP4
Protein: p.Val372Ala
Coding: c.1115T>C
MANE Select: NM_001394
Type: single nucleotide variant
Location: chr8:29337096 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.78 · 1 PDB

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

Similar variants

DUSP4 p.Val372Met Uncertain significance ★ ⚠ same residue
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

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-val372ala (accessed [today's date]).

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