Is DUSP29 p.Val84Met (c.250G>A) pathogenic?

DUSP29 p.Val84Met (c.250G>A) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.7353); Ultra-rare (popmax 0.0457%, nfe).

How common is DUSP29 p.Val84Met (c.250G>A) in the general population?

DUSP29 p.Val84Met (c.250G>A) is ultra-rare (popmax 0.0457%, nfe) (gnomAD).

What do computational predictors say about DUSP29 p.Val84Met (c.250G>A)?

AlphaMissense predicts likely pathogenic (score 0.7353) — an in-silico prediction, not a clinical call.

DUSP29 p.Val84Met

c.250G>A · rs143238854 · VCV3086316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7353 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7353	likely pathogenic
REVEL	0.461	indeterminate
SaProt	LLR -12.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.93, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	29.6	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 0.0457% European (non-Finnish) · 539/1,179,920 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.035% 564/1,613,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0457%	2,189
Remaining individualsnot grpmax-eligible	0.0272%	3,672
African / African-American	0.00666%	15,008
Finnishnot grpmax-eligible	0.0047%	21,271

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: DUSP29
Protein: p.Val84Met
Coding: c.250G>A
MANE Select: NM_001003892
dbSNP: rs143238854
Type: single nucleotide variant
Location: chr10:75043968 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10 · 1 PDB
Residue 84: the tyrosine-protein phosphatase domain; a β-strand

Full DUSP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP29 p.Ala130Thr Uncertain significance ★ ⚠ same type
DUSP29 p.Ala135Glu Uncertain significance ★ ⚠ same type
DUSP29 p.Ala38Asp Uncertain significance ★ ⚠ same type
DUSP29 p.Ala38Gly Uncertain significance ★ ⚠ same type
DUSP29 p.Ala70Ser Uncertain significance ★ ⚠ same type
DUSP29 p.Ala70Val Uncertain significance ★ ⚠ same type
DUSP29 p.Arg151Cys Uncertain significance ★ ⚠ same type
DUSP29 p.Arg151His 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/dusp29-p-val84met (accessed [today's date]).

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