Is DUSP9 p.Ala45Thr (c.133G>A) pathogenic?

DUSP9 p.Ala45Thr (c.133G>A) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: likely benign (0.2207); Absent from gnomAD v4.1.

How common is DUSP9 p.Ala45Thr (c.133G>A) in the general population?

DUSP9 p.Ala45Thr (c.133G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP9 p.Ala45Thr (c.133G>A)?

AlphaMissense predicts likely benign (score 0.2207) — an in-silico prediction, not a clinical call.

DUSP9 p.Ala45Thr

c.133G>A · VCV4245631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2207 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,029,755)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2207	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.71	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	23.5	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

No allele count reported in gnomAD v4.1 (AN 1,029,755). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DUSP9
Protein: p.Ala45Thr
Coding: c.133G>A
MANE Select: NM_001318503
Type: single nucleotide variant
Location: chrX:153648086 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 45: the rhodanese domain

Full DUSP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP9 p.Ala151Val Benign ★★ same type
DUSP9 p.Ala174= Benign ★★ same type
DUSP9 p.Pro158= Benign ★★ same type
DUSP9 p.Ala174Val Uncertain significance ★ ⚠ same type
DUSP9 p.Ala226Ser Uncertain significance ★ ⚠ same type
DUSP9 p.Ala362Val Uncertain significance ★ ⚠ same type
DUSP9 p.Ala48Thr Uncertain significance ★ ⚠ same type
DUSP9 p.Arg145His 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/dusp9-p-ala45thr (accessed [today's date]).

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