Is TREX1 p.Ser3= (c.9G>A) pathogenic?

TREX1 p.Ser3= (c.9G>A) is classified Conflicting classifications of pathogenicity in TREX1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0335%, eas); Associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

How common is TREX1 p.Ser3= (c.9G>A) in the general population?

TREX1 p.Ser3= (c.9G>A) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

TREX1 p.Ser3=

Q: What condition is associated with TREX1 p.Ser3= (c.9G>A)?

TREX1 p.Ser3= (c.9G>A) 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.9G>A · rs762687506 · VCV345772

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, eas)

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 -4.3	GERP -2.9
Overall
CADD	1.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% East Asian · 15/44,836 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00223% 36/1,613,594 alleles · ultra-rare exomes 33/1,461,766 · genomes 3/151,828 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0335%	2,989
Admixed American	0.01%	9,995
African / African-American	0.00134%	74,790
European (non-Finnish)	0.0011%	90,763
South Asian	0.0011%	91,076

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.Ser3=
Coding: c.9G>A
MANE Select: NM_033629
dbSNP: rs762687506
Type: single nucleotide variant
Location: chr3:48466664 (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-ser3 (accessed [today's date]).

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