Is DUSP29 p.Glu67Lys (c.199G>A) pathogenic?

DUSP29 p.Glu67Lys (c.199G>A) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.3676); Very rare (popmax 0.00416%, nfe).

How common is DUSP29 p.Glu67Lys (c.199G>A) in the general population?

DUSP29 p.Glu67Lys (c.199G>A) is very rare (popmax 0.00416%, nfe) (gnomAD).

What do computational predictors say about DUSP29 p.Glu67Lys (c.199G>A)?

AlphaMissense predicts ambiguous (score 0.3676) — an in-silico prediction, not a clinical call.

DUSP29 p.Glu67Lys

c.199G>A · VCV4245567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00416%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3676	ambiguous
REVEL	0.605	indeterminate
SaProt	LLR -6.98	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	25.3	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 0.00416% European (non-Finnish) · 49/1,177,876 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00287%

Overall 0.00329% 53/1,610,846 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00416%	24,038
Admixed American	0.00334%	29,956
Remaining individualsnot grpmax-eligible	0.0016%	62,318
Finnishnot grpmax-eligible	0.00156%	64,000

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.Glu67Lys
Coding: c.199G>A
MANE Select: NM_001003892
Type: single nucleotide variant
Location: chr10:75058316 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10 · 1 PDB
Residue 67: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

DUSP29 p.Glu67Asp Uncertain significance ★ ⚠ same residue
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

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-glu67lys (accessed [today's date]).

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