ITPR1 p.Pro434Ala
c.1300C>G · VCV4534601
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2254 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2254 | likely benign |
|---|---|---|
| REVEL | 0.597 | indeterminate |
| SaProt | — | not scored · why |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 0.18, phastCons 1 |
| Regional constraint | o/e 0.15 | constrained · MANE · 47 bp · p 0.00012 · regional, not allelic |
| Overall | ||
| CADD | 25.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
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
- ITPR1
- Protein
- p.Pro434Ala
- Coding
- c.1300C>G
- MANE Select
- NM_001378452
- Type
- single nucleotide variant
- Location
- chr3:4662130 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 434
- the mir 5 domain
Similar variants
- ITPR1 p.Pro434= Benign/Likely benign ★★ same residue
- ITPR1 c.1252-1G>C Pathogenic/Likely pathogenic ★★ same type
- ITPR1 c.1252-1G>T Pathogenic/Likely pathogenic ★★ same type
- ITPR1 p.Arg241Lys Pathogenic/Likely pathogenic ★★ same type
- ITPR1 p.Arg269Leu Pathogenic/Likely pathogenic ★★ same type
- ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same type
- ITPR1 p.Arg504Gly Likely pathogenic ★★ same type
- ITPR1 p.Arg506Trp 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/itpr1-p-pro434ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown