Is TREX1 p.Phe17= (c.51C>T) pathogenic?

TREX1 p.Phe17= (c.51C>T) is classified Likely benign in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Very rare (popmax 0.00439%, sas); Associated with Aicardi-Goutieres syndrome 1.

How common is TREX1 p.Phe17= (c.51C>T) in the general population?

TREX1 p.Phe17= (c.51C>T) is very rare (popmax 0.00439%, sas) (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.Phe17=

Q: What condition is associated with TREX1 p.Phe17= (c.51C>T)?

TREX1 p.Phe17= (c.51C>T) is associated with Aicardi-Goutieres syndrome 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, chilblain lupus 1 (ClinVar).

c.51C>T · rs1252848366 · VCV2043105

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Aicardi-Goutieres syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP -0.44, phastCons 1
Overall
CADD	15.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,090 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,614,054 alleles · very rare exomes 6/1,461,820 · genomes 0/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Phe17=
Coding: c.51C>T
MANE Select: NM_033629
dbSNP: rs1252848366
Type: single nucleotide variant
Location: chr3:48466706 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.03 · 12 PDB
Residue 17: a β-strand

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.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
TREX1 p.Gln28His Uncertain significance ★★ ⚠ same condition
TREX1 p.Ile84Val Uncertain significance ★★ same condition
TREX1 p.Leu69Pro Uncertain significance ★★ ⚠ same condition
TREX1 p.Phe131Val 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-phe17 (accessed [today's date]).

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