Is DUSP3 p.Val122Ile (c.364G>A) pathogenic?

DUSP3 p.Val122Ile (c.364G>A) is classified Uncertain significance in DUSP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.1876); Ultra-rare (popmax 0.0483%, sas).

How common is DUSP3 p.Val122Ile (c.364G>A) in the general population?

DUSP3 p.Val122Ile (c.364G>A) is ultra-rare (popmax 0.0483%, sas) (gnomAD).

What do computational predictors say about DUSP3 p.Val122Ile (c.364G>A)?

AlphaMissense predicts likely benign (score 0.1876) — an in-silico prediction, not a clinical call.

DUSP3 p.Val122Ile

c.364G>A · rs200022065 · VCV3086327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1876 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1876	likely benign
REVEL	0.497	indeterminate
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,312 bp · p 0.0071 · regional, not allelic
Overall
CADD	28.1	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 0.0483% South Asian · 44/91,072 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00434% 70/1,614,044 alleles · ultra-rare exomes 62/1,461,778 · genomes 8/152,266 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0483%	2,070
African / African-American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0048%	20,833
Admixed American	0.00167%	59,986
European (non-Finnish)	0.00144%	69,412

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.Val122Ile
Coding: c.364G>A
MANE Select: NM_004090
dbSNP: rs200022065
Type: single nucleotide variant
Location: chr17:43769803 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 96.10 · 9 PDB
Residue 122: the tyrosine-protein phosphatase domain; a β-strand

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-val122ile (accessed [today's date]).

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