Is ATRIP p.Thr245fs (c.733del) pathogenic?

ATRIP p.Thr245fs (c.733del) is classified Uncertain significance in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-02). Very rare (popmax 0.0017%, amr).

How common is ATRIP p.Thr245fs (c.733del) in the general population?

ATRIP p.Thr245fs (c.733del) is very rare (popmax 0.0017%, amr) (gnomAD).

ATRIP p.Thr245fs

c.733del · VCV4867203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,794 alleles

Overall 6.88e-05% 1/1,454,264 alleles · very rare

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: ATRIP
Protein: p.Thr245fs
Coding: c.733del
MANE Select: NM_130384
Type: Deletion
Location: chr3:48457316 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB

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

Similar variants

ATRIP p.Thr245Ala Uncertain significance ★ ⚠ same residue
ATRIP p.Thr245Gln Uncertain significance ★ same residue
ATRIP p.Thr245Lys Uncertain significance ★ ⚠ same residue
TREX1 p.Pro245Arg Uncertain significance ★ ⚠ same residue
TREX1 p.Pro245Ser Uncertain significance ★ ⚠ same residue
ATRIP p.Thr245Pro Likely benign ★ same residue
TREX1 p.Pro245= Likely benign ★ same residue
TREX1 p.Ala139fs Pathogenic/Likely pathogenic ★★ same type

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/atrip-p-thr245fs (accessed [today's date]).

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