Is DUSP29 p.Lys166Met (c.497A>T) pathogenic?

DUSP29 p.Lys166Met (c.497A>T) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.3344); Absent from gnomAD v4.1.

How common is DUSP29 p.Lys166Met (c.497A>T) in the general population?

DUSP29 p.Lys166Met (c.497A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP29 p.Lys166Met (c.497A>T)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

DUSP29 p.Lys166Met

c.497A>T · VCV4245568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -11.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP29
Protein: p.Lys166Met
Coding: c.497A>T
MANE Select: NM_001003892
Type: single nucleotide variant
Location: chr10:75038002 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10 · 1 PDB
Residue 166: the tyrosine-protein phosphatase domain

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

Similar variants

DUSP29 p.Lys166Glu Uncertain significance ★ ⚠ same residue
DUSP29 p.Lys166Arg Likely benign ★ 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

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-lys166met (accessed [today's date]).

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