Is TREX1 p.Lys242= (c.726G>A) pathogenic?

TREX1 p.Lys242= (c.726G>A) is classified Likely benign in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). Very rare (popmax 0.00167%, amr); Associated with Aicardi-Goutieres syndrome 1.

What condition is associated with TREX1 p.Lys242= (c.726G>A)?

TREX1 p.Lys242= (c.726G>A) is associated with Aicardi-Goutieres syndrome 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, chilblain lupus 1 (ClinVar).

How common is TREX1 p.Lys242= (c.726G>A) in the general population?

TREX1 p.Lys242= (c.726G>A) is very rare (popmax 0.00167%, amr) (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.Lys242=

c.726G>A · rs1015613176 · VCV2059303

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Aicardi-Goutieres syndrome 1

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 -0.24	GERP -3
Overall
CADD	2.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.000169%	590,019

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.Lys242=
Coding: c.726G>A
MANE Select: NM_130384 · reported on NM_033629
dbSNP: rs1015613176
Type: single nucleotide variant
Location: chr3:48467381 (GRCh38)

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)

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-lys242 (accessed [today's date]).

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