Is TREX1 p.Asp200His (c.598G>C) pathogenic?

TREX1 p.Asp200His (c.598G>C) is classified Likely pathogenic in TREX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.9514); Absent from gnomAD v4.1; Associated with TREX1-related disorder.

What condition is associated with TREX1 p.Asp200His (c.598G>C)?

TREX1 p.Asp200His (c.598G>C) is associated with TREX1-related disorder (ClinVar).

How common is TREX1 p.Asp200His (c.598G>C) in the general population?

TREX1 p.Asp200His (c.598G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TREX1 p.Asp200His (c.598G>C)?

AlphaMissense predicts likely pathogenic (score 0.9514) — an in-silico prediction, not a clinical call.

TREX1 p.Asp200His

c.598G>C · VCV4855591

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TREX1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9514	likely pathogenic ✓ concordant with ClinVar
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -12.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 941 bp · p 0.82 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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.Asp200His
Coding: c.598G>C
MANE Select: NM_130384 · reported on NM_033629
Type: single nucleotide variant
Location: chr3:48467253 (GRCh38)

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

Disease context

TREX1-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp200his (accessed [today's date]).

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