Is DUSP10 p.Pro447Leu (c.1340C>T) pathogenic?

DUSP10 p.Pro447Leu (c.1340C>T) is classified Uncertain significance in DUSP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1.

How common is DUSP10 p.Pro447Leu (c.1340C>T) in the general population?

DUSP10 p.Pro447Leu (c.1340C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP10 p.Pro447Leu (c.1340C>T)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

DUSP10 p.Pro447Leu

c.1340C>T · VCV4245469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic · top 3% in DUSP10
REVEL	0.701	pathogenic-leaning
SaProt	LLR -13.99	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 37 kb · p 0.0053 · 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

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: DUSP10
Protein: p.Pro447Leu
Coding: c.1340C>T
MANE Select: NM_007207
Type: single nucleotide variant
Location: chr1:221702521 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 70.95 · 23 PDB
Residue 447: the tyrosine-protein phosphatase domain

Full DUSP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP10 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala300Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala47Val Uncertain significance ★ ⚠ same type
DUSP10 p.Ala55Pro Uncertain significance ★ ⚠ same type
DUSP10 p.Ala99Ser Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Gln Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Trp Uncertain significance ★ ⚠ same type
DUSP10 p.Arg245Leu 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/dusp10-p-pro447leu (accessed [today's date]).

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