Is DUSP19 p.Ser127Pro (c.379T>C) pathogenic?

DUSP19 p.Ser127Pro (c.379T>C) is classified Uncertain significance in DUSP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.1305); Absent from gnomAD v4.1.

How common is DUSP19 p.Ser127Pro (c.379T>C) in the general population?

DUSP19 p.Ser127Pro (c.379T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP19 p.Ser127Pro (c.379T>C)?

AlphaMissense predicts likely benign (score 0.1305) — an in-silico prediction, not a clinical call.

DUSP19 p.Ser127Pro

c.379T>C · VCV4015395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1305 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1305	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -12.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.32	acceptor loss, 13 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.1	GERP 0.53, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.9 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP19
Protein: p.Ser127Pro
Coding: c.379T>C
MANE Select: NM_080876
Type: single nucleotide variant
Location: chr2:183087145 (GRCh38)
Gene constraint: LOEUF 1.516 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.39 · 4 PDB
Residue 127: the tyrosine-protein phosphatase domain; an α-helix

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-ser127pro (accessed [today's date]).

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