Is TREX1 p.Pro8= (c.24G>A) pathogenic?

TREX1 p.Pro8= (c.24G>A) is classified Likely benign in TREX1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). Ultra-rare (popmax 0.0117%, amr); Associated with chilblain lupus 1.

How common is TREX1 p.Pro8= (c.24G>A) in the general population?

TREX1 p.Pro8= (c.24G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Familial Chilblain lupus inherited?

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

TREX1 p.Pro8=

Q: What condition is associated with TREX1 p.Pro8= (c.24G>A)?

TREX1 p.Pro8= (c.24G>A) is associated with chilblain lupus 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, Aicardi-Goutieres syndrome 1 (ClinVar).

c.24G>A · rs147463121 · VCV844413

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

chilblain lupus 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 -13	GERP -3.5
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,952 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00198% 32/1,613,506 alleles · ultra-rare exomes 28/1,461,784 · genomes 4/151,722 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,565
Remaining individualsnot grpmax-eligible	0.008%	12,496
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
Finnishnot grpmax-eligible	0.00313%	31,954
African / African-American	0.00268%	37,359
European (non-Finnish)	0.00119%	84,281

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.Pro8=
Coding: c.24G>A
MANE Select: NM_033629
dbSNP: rs147463121
Type: single nucleotide variant
Location: chr3:48466679 (GRCh38)

Full TREX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

chilblain lupus 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Aicardi-Goutieres syndrome 1

For Familial Chilblain lupus (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

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-pro8 (accessed [today's date]).

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