Is DUSP29 p.Thr35Ala (c.103A>G) pathogenic?

DUSP29 p.Thr35Ala (c.103A>G) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: ambiguous (0.4084); Ultra-rare (popmax 0.0453%, afr).

How common is DUSP29 p.Thr35Ala (c.103A>G) in the general population?

DUSP29 p.Thr35Ala (c.103A>G) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about DUSP29 p.Thr35Ala (c.103A>G)?

AlphaMissense predicts ambiguous (score 0.4084) — an in-silico prediction, not a clinical call.

DUSP29 p.Thr35Ala

c.103A>G · VCV4662567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4084	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.54, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	22.0	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 0.0453% African / African-American · 34/75,042 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.00235% 38/1,614,174 alleles · ultra-rare exomes 17/1,461,890 · genomes 21/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	8.47e-05%	1,180,011

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.Thr35Ala
Coding: c.103A>G
MANE Select: NM_001003892
Type: single nucleotide variant
Location: chr10:75058412 (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.Thr35Asn 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-thr35ala (accessed [today's date]).

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