Sugi Variant
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TREX1/p.Pro25Arg

TREX1 p.Pro25Arg

c.74C>G · VCV3763559

Uncertain significance Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4834 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
3
retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense0.4834ambiguous
REVEL0.594indeterminate
SaProtLLR -7.71tolerated
Splicing
SpliceAI—not looked up on this page · why
Constraint at this position
ConservationphyloP 7.6GERP 1.8, phastCons 1
Regional constrainto/e 1.01unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD27.6PHRED · 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
TREX1
Protein
p.Pro25Arg
Coding
c.74C>G
MANE Select
NM_033629
Type
single nucleotide variant
Location
chr3:48466729 (GRCh38)
Full TREX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Aicardi-Goutieres syndrome 1chilblain lupus 1

For Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (Orphanet):

Inheritance
Autosomal dominant
Onset
Adult, Elderly

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/trex1-p-pro25arg (accessed [today's date]).

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