Is ATRIP p.Arg760Ter (c.2278C>T) pathogenic?

ATRIP p.Arg760Ter (c.2278C>T) is classified Uncertain significance in ATRIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-01-01). Very rare (popmax 0.0011%, sas).

How common is ATRIP p.Arg760Ter (c.2278C>T) in the general population?

ATRIP p.Arg760Ter (c.2278C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ATRIP p.Arg760Ter

c.2278C>T · rs587777856 · VCV156542

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 30 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.8	GERP 1.5, phastCons 1
Overall
CADD	53.0	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 0.0011% South Asian · 1/91,056 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,612,750 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00157%	63,688
South Asiangrpmax	0.0011%	91,056
European (non-Finnish)	0.000424%	235,853

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg760Ter
Coding: c.2278C>T
MANE Select: NM_130384
dbSNP: rs587777856
Type: single nucleotide variant
Location: chr3:48465053 (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.Arg760Gln Uncertain significance ★ ⚠ same residue
ATRIP p.Arg760= Likely benign ★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Asp18Asn Pathogenic ★★ same type
TREX1 p.Asp200His Likely pathogenic ★★ same type
TREX1 p.Gln135Ter Pathogenic/Likely pathogenic ★★ same type
ATRIP p.Ala119Thr Uncertain significance ★★ ⚠ 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-arg760ter (accessed [today's date]).

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