Is ATRIP p.Pro235fs (c.701dup) pathogenic?

ATRIP p.Pro235fs (c.701dup) is classified Uncertain significance in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Very rare (popmax 0.00135%, afr).

How common is ATRIP p.Pro235fs (c.701dup) in the general population?

ATRIP p.Pro235fs (c.701dup) is very rare (popmax 0.00135%, afr) (gnomAD).

ATRIP p.Pro235fs

c.701dup · VCV3975902

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 0.00135%, afr)

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 1.2	GERP -0.13, phastCons 0.37
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/73,806 alleles

Overall 0.000657% 1/152,236 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.Pro235fs
Coding: c.701dup
MANE Select: NM_130384
Type: Duplication
Location: chr3:48457285 (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.Pro235Leu Uncertain significance ★★ ⚠ same residue
ATRIP p.Pro235Ala Uncertain significance ★ ⚠ same residue
ATRIP p.Pro235Ser Uncertain significance ★ ⚠ same residue
TREX1 p.Val235fs Conflicting classifications of pathogenicity ★ same residue
TREX1 p.Val235Gly Uncertain significance ★ ⚠ same residue
TREX1 p.Val235= Likely benign ★ same residue
TREX1 p.Asp200dup Likely pathogenic ★★ same type
TREX1 p.Cys42Ter 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-pro235fs (accessed [today's date]).

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