Is DUSP3 p.Ile109Val (c.325A>G) pathogenic?

DUSP3 p.Ile109Val (c.325A>G) is classified Uncertain significance in DUSP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely benign (0.2653); Ultra-rare (popmax 0.0296%, sas).

How common is DUSP3 p.Ile109Val (c.325A>G) in the general population?

DUSP3 p.Ile109Val (c.325A>G) is ultra-rare (popmax 0.0296%, sas) (gnomAD).

What do computational predictors say about DUSP3 p.Ile109Val (c.325A>G)?

AlphaMissense predicts likely benign (score 0.2653) — an in-silico prediction, not a clinical call.

DUSP3 p.Ile109Val

c.325A>G · rs751046817 · VCV3086326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2653 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2653	likely benign
REVEL	0.698	pathogenic-leaning
SaProt	LLR -6.16	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,312 bp · p 0.0071 · regional, not allelic
Overall
CADD	25.9	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 0.0296% South Asian · 27/91,088 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00229% 37/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0296%	3,374
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.000593%	168,577

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: DUSP3
Protein: p.Ile109Val
Coding: c.325A>G
MANE Select: NM_004090
dbSNP: rs751046817
Type: single nucleotide variant
Location: chr17:43774739 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 96.10 · 9 PDB
Residue 109: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP3 p.Arg104Thr Uncertain significance ★ ⚠ same type
DUSP3 p.Arg119Gln Uncertain significance ★ ⚠ same type
DUSP3 p.Arg125Trp Uncertain significance ★ ⚠ same type
DUSP3 p.Arg158Cys Uncertain significance ★ ⚠ same type
DUSP3 p.Asn174Ser Uncertain significance ★ ⚠ same type
DUSP3 p.Asn74Ser Uncertain significance ★ ⚠ same type
DUSP3 p.Asp164Tyr Uncertain significance ★ ⚠ same type
DUSP3 p.Gln10Glu 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/dusp3-p-ile109val (accessed [today's date]).

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