Is TREX1 p.Pro55Ser (c.163C>T) pathogenic?

TREX1 p.Pro55Ser (c.163C>T) is classified Uncertain significance in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-29). AlphaMissense: likely benign (0.0712); Absent from gnomAD v4.1; Associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

How common is TREX1 p.Pro55Ser (c.163C>T) in the general population?

TREX1 p.Pro55Ser (c.163C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TREX1 p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

TREX1 p.Pro55Ser

Q: What condition is associated with TREX1 p.Pro55Ser (c.163C>T)?

TREX1 p.Pro55Ser (c.163C>T) is associated with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, Aicardi-Goutieres syndrome 1, chilblain lupus 1 (ClinVar).

Q: How is Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations inherited?

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

c.163C>T · VCV3752624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

⚠ 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	0.0712	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -3.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Regional constraint	o/e 1.01	unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD	6.791	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

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.Pro55Ser
Coding: c.163C>T
MANE Select: NM_033629
Type: single nucleotide variant
Location: chr3:48466818 (GRCh38)

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

Disease context

retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Aicardi-Goutieres syndrome 1 chilblain lupus 1

For Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

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-pro55ser (accessed [today's date]).

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