Is DUSP3 p.Glu180Lys (c.538G>A) pathogenic?

DUSP3 p.Glu180Lys (c.538G>A) is classified Uncertain significance in DUSP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.2359); Very rare (popmax 0.00133%, afr).

How common is DUSP3 p.Glu180Lys (c.538G>A) in the general population?

DUSP3 p.Glu180Lys (c.538G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DUSP3 p.Glu180Lys (c.538G>A)?

AlphaMissense predicts likely benign (score 0.2359) — an in-silico prediction, not a clinical call.

DUSP3 p.Glu180Lys

c.538G>A · VCV3505897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2359	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,312 bp · p 0.0071 · regional, not allelic
Overall
CADD	23.8	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 0.00133% African / African-American · 1/74,990 alleles

Overall 0.000137% 2/1,459,914 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,990
European (non-Finnish)	8.48e-05%	1,179,848

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.Glu180Lys
Coding: c.538G>A
MANE Select: NM_004090
Type: single nucleotide variant
Location: chr17:43769629 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 96.10 · 9 PDB

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.Arg158Cys 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

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-glu180lys (accessed [today's date]).

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