Is DUSP4 p.Pro178Ala (c.532C>G) pathogenic?

DUSP4 p.Pro178Ala (c.532C>G) is classified Uncertain significance in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0587); Ultra-rare (popmax 0.019%, sas).

How common is DUSP4 p.Pro178Ala (c.532C>G) in the general population?

DUSP4 p.Pro178Ala (c.532C>G) is ultra-rare (popmax 0.019%, sas) (gnomAD).

What do computational predictors say about DUSP4 p.Pro178Ala (c.532C>G)?

AlphaMissense predicts likely benign (score 0.0587) — an in-silico prediction, not a clinical call.

DUSP4 p.Pro178Ala

c.532C>G · rs767394125 · VCV3086335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0587	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.43	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 0.065	GERP -3.4, phastCons 0.33
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.014 · regional, not allelic
Overall
CADD	15.05	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

Grpmax group 0.019% South Asian · 17/89,502 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00992%

Overall 0.00778% 125/1,605,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.019%	5,265
European (non-Finnish)	0.0085%	11,761
Admixed American	0.00513%	19,511
Remaining individualsnot grpmax-eligible	0.00482%	20,765
Finnishnot grpmax-eligible	0.00158%	63,438
African / African-American	0.00133%	74,936

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.Pro178Ala
Coding: c.532C>G
MANE Select: NM_001394
dbSNP: rs767394125
Type: single nucleotide variant
Location: chr8:29340145 (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-pro178ala (accessed [today's date]).

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