Is TREX1 p.Arg284fs (c.850dup) pathogenic?

TREX1 p.Arg284fs (c.850dup) is classified Likely pathogenic in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). Associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

TREX1 p.Arg284fs

Q: What condition is associated with TREX1 p.Arg284fs (c.850dup)?

TREX1 p.Arg284fs (c.850dup) is associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (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.850dup · VCV3376804

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.72	GERP -2.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TREX1
Protein: p.Arg284fs
Coding: c.850dup
MANE Select: NM_130384 · reported on NM_033629
Type: Duplication
Location: chr3:48467504 (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

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-arg284fs (accessed [today's date]).

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