Is ATRIP p.Pro30Arg (c.89C>G) pathogenic?

ATRIP p.Pro30Arg (c.89C>G) is classified Uncertain significance in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.2757); Very rare (popmax 0.000271%, nfe).

How common is ATRIP p.Pro30Arg (c.89C>G) in the general population?

ATRIP p.Pro30Arg (c.89C>G) is very rare (popmax 0.000271%, nfe) (gnomAD).

What do computational predictors say about ATRIP p.Pro30Arg (c.89C>G)?

AlphaMissense predicts likely benign (score 0.2757) — an in-silico prediction, not a clinical call.

ATRIP p.Pro30Arg

c.89C>G · VCV3808968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2757	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.76, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000271% European (non-Finnish) · 3/1,107,168 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000229% 3/1,309,816 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.Pro30Arg
Coding: c.89C>G
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48446934 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 30: the 'disordered' region

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

Similar variants

ATRIP p.Pro30Ser Uncertain significance ★★ ⚠ same residue
ATRIP p.Pro30Gln Uncertain significance ★ ⚠ same residue
ATRIP p.Pro30Leu Uncertain significance ★ ⚠ same residue
ATRIP p.Pro30Thr Uncertain significance ★ ⚠ same residue
TREX1 p.Lys30Glu Uncertain significance ★ ⚠ same residue
ATRIP p.Pro30= Likely benign ★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter 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-pro30arg (accessed [today's date]).

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