Is DUSP19 p.Gly67Arg (c.199G>C) pathogenic?

DUSP19 p.Gly67Arg (c.199G>C) is classified Uncertain significance in DUSP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely pathogenic (0.9398); Ultra-rare (popmax 0.0227%, afr).

How common is DUSP19 p.Gly67Arg (c.199G>C) in the general population?

DUSP19 p.Gly67Arg (c.199G>C) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about DUSP19 p.Gly67Arg (c.199G>C)?

AlphaMissense predicts likely pathogenic (score 0.9398) — an in-silico prediction, not a clinical call.

DUSP19 p.Gly67Arg

c.199G>C · rs140895775 · VCV2260527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9398 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9398	likely pathogenic
REVEL	0.449	indeterminate
SaProt	LLR -11.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.9 · regional, not allelic
Overall
CADD	32.0	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 0.0227% African / African-American · 17/74,992 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00105% 17/1,613,908 alleles · ultra-rare exomes 5/1,461,694 · genomes 12/152,214 · joint denominator

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.Gly67Arg
Coding: c.199G>C
MANE Select: NM_080876
dbSNP: rs140895775
Type: single nucleotide variant
Location: chr2:183079132 (GRCh38)
Gene constraint: LOEUF 1.516 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.39 · 4 PDB
Residue 67: the tyrosine-protein phosphatase domain; a β-strand

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

Similar variants

DUSP19 p.Gly67Ala Uncertain significance ★ ⚠ same residue
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

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-gly67arg (accessed [today's date]).

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