Is DUSP29 p.Arg209His (c.626G>A) pathogenic?

DUSP29 p.Arg209His (c.626G>A) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0689); Ultra-rare (popmax 0.0111%, eas).

How common is DUSP29 p.Arg209His (c.626G>A) in the general population?

DUSP29 p.Arg209His (c.626G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about DUSP29 p.Arg209His (c.626G>A)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

DUSP29 p.Arg209His

c.626G>A · VCV4245570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -8.40	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 -1.5	GERP -3.6
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	0.076	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 0.0111% East Asian · 5/44,846 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0013% 21/1,611,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,969
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0033%	30,343
Remaining individualsnot grpmax-eligible	0.0032%	31,227
African / African-American	0.00133%	75,038
European (non-Finnish)	0.000763%	131,033

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.Arg209His
Coding: c.626G>A
MANE Select: NM_001003892
Type: single nucleotide variant
Location: chr10:75037873 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10 · 1 PDB

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

Similar variants

DUSP29 p.Arg209Pro Uncertain significance ★ ⚠ same residue
DUSP29 p.Arg209Cys 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-arg209his (accessed [today's date]).

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