Is TREX1 p.Leu37Pro (c.110T>C) pathogenic?

TREX1 p.Leu37Pro (c.110T>C) is classified Uncertain significance in TREX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.919); Absent from gnomAD v4.1; Associated with chilblain lupus 1.

How common is TREX1 p.Leu37Pro (c.110T>C) in the general population?

TREX1 p.Leu37Pro (c.110T>C) is absent from gnomAD v4.1 (gnomAD).

How is Familial Chilblain lupus inherited?

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

What do computational predictors say about TREX1 p.Leu37Pro (c.110T>C)?

AlphaMissense predicts likely pathogenic (score 0.919) — an in-silico prediction, not a clinical call.

TREX1 p.Leu37Pro

Q: What condition is associated with TREX1 p.Leu37Pro (c.110T>C)?

TREX1 p.Leu37Pro (c.110T>C) is associated with chilblain lupus 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, Aicardi-Goutieres syndrome 1 (ClinVar).

c.110T>C · VCV4785908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.919 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chilblain lupus 1

Computational evidence

Protein change
AlphaMissense	0.919	likely pathogenic
REVEL	0.772	pathogenic-leaning
SaProt	LLR -15.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Leu37Pro
Coding: c.110T>C
MANE Select: NM_130384 · reported on NM_033629
Type: single nucleotide variant
Location: chr3:48466765 (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-leu37pro (accessed [today's date]).

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