Is DUSP19 p.Val92Met (c.274G>A) pathogenic?

DUSP19 p.Val92Met (c.274G>A) is classified Uncertain significance in DUSP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.8952); Very rare (popmax 0.00865%, nfe).

How common is DUSP19 p.Val92Met (c.274G>A) in the general population?

DUSP19 p.Val92Met (c.274G>A) is very rare (popmax 0.00865%, nfe) (gnomAD).

What do computational predictors say about DUSP19 p.Val92Met (c.274G>A)?

AlphaMissense predicts likely pathogenic (score 0.8952) — an in-silico prediction, not a clinical call.

DUSP19 p.Val92Met

c.274G>A · VCV3505858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00865%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8952	likely pathogenic
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -15.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.9 · regional, not allelic
Overall
CADD	33.0	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 0.00865% European (non-Finnish) · 102/1,178,732 alleles

Filtering AF 0.00725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00677%

Overall 0.00666% 107/1,607,338 alleles · very rare exomes 94/1,455,224 · genomes 13/152,114 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00865%	11,556
Remaining individualsnot grpmax-eligible	0.00321%	31,158
Finnishnot grpmax-eligible	0.00162%	61,836
African / African-American	0.00134%	74,822
South Asian	0.00112%	89,378

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: DUSP19
Protein: p.Val92Met
Coding: c.274G>A
MANE Select: NM_080876
Type: single nucleotide variant
Location: chr2:183087040 (GRCh38)
Gene constraint: LOEUF 1.516 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.39 · 4 PDB
Residue 92: the tyrosine-protein phosphatase domain

Full DUSP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP19 p.Ala10Val Uncertain significance ★ ⚠ same type
DUSP19 p.Arg141Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198Cys Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198His Uncertain significance ★ ⚠ same type
DUSP19 p.Arg211Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Asn167Ser Uncertain significance ★ ⚠ same type
DUSP19 p.Asp143Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Asp37Gly 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/dusp19-p-val92met (accessed [today's date]).

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