Is TREX1 p.Pro10= (c.30C>T) pathogenic?

TREX1 p.Pro10= (c.30C>T) is classified Likely benign in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Very rare (popmax 0.0011%, sas); Associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

How common is TREX1 p.Pro10= (c.30C>T) in the general population?

TREX1 p.Pro10= (c.30C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TREX1 p.Pro10=

Q: What condition is associated with TREX1 p.Pro10= (c.30C>T)?

TREX1 p.Pro10= (c.30C>T) is associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, Aicardi-Goutieres syndrome 1, chilblain lupus 1 (ClinVar).

Q: How is Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.30C>T · rs560658691 · VCV1661016

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.6	GERP -3.2
Overall
CADD	6.441	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 6.2e-05% 1/1,614,070 alleles · very rare exomes 0/1,461,800 · genomes 1/152,270 · 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: TREX1
Protein: p.Pro10=
Coding: c.30C>T
MANE Select: NM_033629
dbSNP: rs560658691
Type: single nucleotide variant
Location: chr3:48466685 (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 1 chilblain 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-pro10 (accessed [today's date]).

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