Is DUSP9 p.Glu96Ala (c.287A>C) pathogenic?

DUSP9 p.Glu96Ala (c.287A>C) is classified Uncertain significance in DUSP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.0653); Very rare (popmax 0.00132%, nfe).

How common is DUSP9 p.Glu96Ala (c.287A>C) in the general population?

DUSP9 p.Glu96Ala (c.287A>C) is very rare (popmax 0.00132%, nfe) (gnomAD).

What do computational predictors say about DUSP9 p.Glu96Ala (c.287A>C)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

DUSP9 p.Glu96Ala

c.287A>C · rs2148321940 · VCV2400160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00132%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -8.22	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 4.7	GERP -0.31, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,348 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	16.73	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 0.00132% European (non-Finnish) · 11/833,872 alleles

Filtering AF 0.000708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000517%

Overall 0.00164% 16/975,616 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0178%	5,623
European (non-Finnish)grpmax	0.00132%	75,806

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DUSP9
Protein: p.Glu96Ala
Coding: c.287A>C
MANE Select: NM_001318503
dbSNP: rs2148321940
Type: single nucleotide variant
Location: chrX:153648240 (GRCh38)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 96: 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.Ala45Thr Uncertain significance ★ ⚠ same type
DUSP9 p.Ala48Thr 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-glu96ala (accessed [today's date]).

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