Is TREX1 p.Pro79fs (c.236_243del) pathogenic?

TREX1 p.Pro79fs (c.236243del) is classified Pathogenic in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-28). Very rare (popmax 0.000508%, nfe); Associated with Aicardi-Goutieres syndrome 1.

What condition is associated with TREX1 p.Pro79fs (c.236_243del)?

TREX1 p.Pro79fs (c.236_243del) is associated with Aicardi-Goutieres syndrome 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, chilblain lupus 1 (ClinVar).

How common is TREX1 p.Pro79fs (c.236_243del) in the general population?

TREX1 p.Pro79fs (c.236_243del) is very rare (popmax 0.000508%, nfe) (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

TREX1 p.Pro79fs

c.236_243del · rs1331920811 · VCV850507

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

Aicardi-Goutieres syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -3.6, phastCons 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,024 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,460,730 alleles · very rare

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.Pro79fs
Coding: c.236_243del
MANE Select: NM_033629
dbSNP: rs1331920811
Type: Microsatellite
Location: chr3:48466882 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.03 · 12 PDB
Residue 79: an α-helix

Full TREX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Aicardi-Goutieres syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations chilblain lupus 1

For Aicardi-Goutières syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

TREX1 p.Ser82fs Pathogenic ★★ same condition
TREX1 p.Val71fs Pathogenic ★★ same condition
TREX1 p.Glu137fs Likely pathogenic ★★ same condition
TREX1 p.Ser167fs Pathogenic/Likely pathogenic ★★ same condition
TREX1 p.Ala150Thr Uncertain significance ★★ ⚠ same condition
TREX1 p.Ala43Thr Uncertain significance ★★ ⚠ same condition
TREX1 p.Asp130Asn Uncertain significance ★★ ⚠ same condition
TREX1 p.Gln209His Uncertain significance ★★ same condition

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-pro79fs (accessed [today's date]).

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