Is DUSP29 p.Ala130Thr (c.388G>A) pathogenic?

DUSP29 p.Ala130Thr (c.388G>A) is classified Uncertain significance in DUSP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0758); Ultra-rare (popmax 0.0174%, afr).

How common is DUSP29 p.Ala130Thr (c.388G>A) in the general population?

DUSP29 p.Ala130Thr (c.388G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about DUSP29 p.Ala130Thr (c.388G>A)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

DUSP29 p.Ala130Thr

c.388G>A · VCV4662566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.11	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 0.26	GERP -3.2, phastCons 0.008
Regional constraint	o/e 1.02	unconstrained · MANE · 21 kb · p 0.69 · regional, not allelic
Overall
CADD	8.554	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 0.0174% African / African-American · 13/74,912 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00174% 28/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
Remaining individualsnot grpmax-eligible	0.00961%	10,411
Admixed American	0.00333%	30,005
South Asian	0.0011%	91,082
European (non-Finnish)	0.000509%	196,654

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.Ala130Thr
Coding: c.388G>A
MANE Select: NM_001003892
Type: single nucleotide variant
Location: chr10:75043830 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10 · 1 PDB
Residue 130: 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.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
DUSP29 p.Arg181Cys 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-ala130thr (accessed [today's date]).

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