Is TREX1 p.Pro61= (c.183G>A) pathogenic?

TREX1 p.Pro61= (c.183G>A) is classified Conflicting classifications of pathogenicity in TREX1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0225%, nfe); Associated with Aicardi-Goutieres syndrome 1.

What condition is associated with TREX1 p.Pro61= (c.183G>A)?

TREX1 p.Pro61= (c.183G>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.Pro61= (c.183G>A) in the general population?

TREX1 p.Pro61= (c.183G>A) is ultra-rare (popmax 0.0225%, 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.Pro61=

c.183G>A · rs55852466 · VCV345773

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, nfe)

Conditions

Aicardi-Goutieres syndrome 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -0.92	GERP -3.2, phastCons 0.002
Overall
CADD	2.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0225% European (non-Finnish) · 265/1,180,018 alleles

Filtering AF 0.0202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0279% 451/1,613,908 alleles · ultra-rare exomes 399/1,461,664 · genomes 52/152,244 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.251%	399
Remaining individualsnot grpmax-eligible	0.0272%	3,677
European (non-Finnish)grpmax	0.0225%	4,453
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
South Asian	0.00329%	30,360
African / African-American	0.00267%	37,512
East Asian	0.00223%	44,868
Admixed American	0.00167%	60,014

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro61=
Coding: c.183G>A
MANE Select: NM_033629
dbSNP: rs55852466
Type: single nucleotide variant
Location: chr3:48466838 (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-pro61 (accessed [today's date]).

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