Is DUSP4 p.Thr188Ala (c.562A>G) pathogenic?

DUSP4 p.Thr188Ala (c.562A>G) is classified Uncertain significance in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.4041); Very rare (popmax 0.0012%, nfe).

How common is DUSP4 p.Thr188Ala (c.562A>G) in the general population?

DUSP4 p.Thr188Ala (c.562A>G) is very rare (popmax 0.0012%, nfe) (gnomAD).

What do computational predictors say about DUSP4 p.Thr188Ala (c.562A>G)?

AlphaMissense predicts ambiguous (score 0.4041) — an in-silico prediction, not a clinical call.

DUSP4 p.Thr188Ala

c.562A>G · VCV4245582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4041	ambiguous
REVEL	0.16	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.014 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.0012% European (non-Finnish) · 14/1,162,900 alleles

Filtering AF 0.000699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000547%

Overall 0.000886% 14/1,580,504 alleles · very rare

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.Thr188Ala
Coding: c.562A>G
MANE Select: NM_001394
Type: single nucleotide variant
Location: chr8:29340115 (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.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.Arg313His 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-thr188ala (accessed [today's date]).

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