Is TREX1 p.Ser82fs (c.243_246del) pathogenic?

TREX1 p.Ser82fs (c.243246del) is classified Pathogenic in TREX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-12). Very rare (popmax 6.85e-05%); Associated with Aicardi-Goutieres syndrome 1.

What condition is associated with TREX1 p.Ser82fs (c.243_246del)?

TREX1 p.Ser82fs (c.243_246del) is associated with Aicardi-Goutieres syndrome 1 (ClinVar).

How common is TREX1 p.Ser82fs (c.243_246del) in the general population?

TREX1 p.Ser82fs (c.243_246del) is very rare (popmax 6.85e-05%) (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.Ser82fs

c.243_246del · rs2040335386 · VCV915280

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

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 3.4	GERP -3.6, phastCons 0.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,028 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.Ser82fs
Coding: c.243_246del
MANE Select: NM_033629
dbSNP: rs2040335386
Type: Microsatellite
Location: chr3:48466894 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.03 · 12 PDB
Residue 82: 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

For Aicardi-Goutières syndrome (Orphanet):

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

Similar variants

TREX1 p.Val71fs Pathogenic ★★ same condition
TREX1 p.Pro79fs 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-ser82fs (accessed [today's date]).

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