Is TREX1 p.Val201Asp (c.602T>A) pathogenic?

TREX1 p.Val201Asp (c.602T>A) is classified Pathogenic in TREX1 (ClinVar, Single submitter, 3 submitters; last evaluated 2019-11-01). AlphaMissense: likely pathogenic (0.9294); Absent from gnomAD v4.1; Associated with Aicardi-Goutieres syndrome 1.

What condition is associated with TREX1 p.Val201Asp (c.602T>A)?

TREX1 p.Val201Asp (c.602T>A) is associated with Aicardi-Goutieres syndrome 1 (ClinVar).

How common is TREX1 p.Val201Asp (c.602T>A) in the general population?

TREX1 p.Val201Asp (c.602T>A) is absent from gnomAD v4.1 (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

What do computational predictors say about TREX1 p.Val201Asp (c.602T>A)?

AlphaMissense predicts likely pathogenic (score 0.9294) — an in-silico prediction, not a clinical call.

TREX1 p.Val201Asp

c.602T>A · rs78408272 · VCV4182

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Aicardi-Goutieres syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9294	likely pathogenic ✓ concordant with ClinVar
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TREX1
Protein: p.Val201Asp
Coding: c.602T>A
MANE Select: NM_033629
dbSNP: rs78408272
Type: single nucleotide variant
Location: chr3:48467257 (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

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-val201asp (accessed [today's date]).

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