Is TREX1 p.Pro262Ser (c.784C>T) pathogenic?

TREX1 p.Pro262Ser (c.784C>T) is classified Uncertain significance in TREX1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-02). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

How common is TREX1 p.Pro262Ser (c.784C>T) in the general population?

TREX1 p.Pro262Ser (c.784C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about TREX1 p.Pro262Ser (c.784C>T)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

TREX1 p.Pro262Ser

Q: What condition is associated with TREX1 p.Pro262Ser (c.784C>T)?

TREX1 p.Pro262Ser (c.784C>T) is associated with Inborn genetic diseases, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, Aicardi-Goutieres syndrome 1 (ClinVar).

c.784C>T · rs867148059 · VCV665857

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ 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
AlphaMissense	0.0727	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.6	GERP -2.7
Regional constraint	o/e 1.01	unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD	8.658	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000434% 7/1,614,068 alleles · ultra-rare exomes 6/1,461,872 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,977
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Admixed American	0.00167%	60,010

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.Pro262Ser
Coding: c.784C>T
MANE Select: NM_033629
dbSNP: rs867148059
Type: single nucleotide variant
Location: chr3:48467439 (GRCh38)

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

Disease context

Inborn genetic diseases — 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 chilblain lupus 1

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-pro262ser (accessed [today's date]).

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