Is DUSP2 p.Gly131Val (c.392G>T) pathogenic?

DUSP2 p.Gly131Val (c.392G>T) is classified Uncertain significance in DUSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.9311); Ultra-rare (popmax 0.0652%, amr).

How common is DUSP2 p.Gly131Val (c.392G>T) in the general population?

DUSP2 p.Gly131Val (c.392G>T) is ultra-rare (popmax 0.0652%, amr) (gnomAD).

What do computational predictors say about DUSP2 p.Gly131Val (c.392G>T)?

AlphaMissense predicts likely pathogenic (score 0.9311) — an in-silico prediction, not a clinical call.

DUSP2 p.Gly131Val

c.392G>T · rs779039146 · VCV2297081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0652%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9311	likely pathogenic
REVEL	0.771	pathogenic-leaning
SaProt	LLR -19.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,528 bp · p 0.41 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0652% Admixed American · 33/50,588 alleles

Filtering AF 0.0477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.0031% 48/1,548,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0652%	1,533
Remaining individualsnot grpmax-eligible	0.00167%	59,972
European (non-Finnish)	0.00122%	81,822

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: DUSP2
Protein: p.Gly131Val
Coding: c.392G>T
MANE Select: NM_004418
dbSNP: rs779039146
Type: single nucleotide variant
Location: chr2:96144879 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.59 · 1 PDB
Residue 131: the rhodanese domain

Full DUSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP2 p.Ala107Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala265Pro Uncertain significance ★ ⚠ same type
DUSP2 p.Ala265Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala45Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala65Gly Uncertain significance ★ ⚠ same type
DUSP2 p.Arg263Cys Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26His Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26Ser 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/dusp2-p-gly131val (accessed [today's date]).

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