ITPR2 p.Gln565Lys
c.1693C>A · VCV4088808
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1888 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, REVEL · SaProt no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1888 | likely benign |
|---|---|---|
| REVEL | 0.668 | pathogenic-leaning |
| SaProt | — | not scored · why |
| ⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.65 | unconstrained · MANE · 175 kb · p 1.6e-22 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | 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
- ITPR2
- Protein
- p.Gln565Lys
- Coding
- c.1693C>A
- MANE Select
- NM_002223
- Type
- single nucleotide variant
- Location
- chr12:26663705 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
Similar variants
- ITPR2 p.Gln565His Uncertain significance ★ same residue
- ITPR2 p.Val1162Gly Uncertain significance ★★ same type
- ITPR2 c.3801+23G>A Benign ★★ same type
- ITPR2 c.5073+10T>A Benign ★★ same type
- ITPR2 c.93-10T>A Benign ★★ same type
- ITPR2 p.Ala1898Val Benign ★★ same type
- ITPR2 p.Arg1180Gln Likely benign ★★ same type
- ITPR2 p.Arg1275Gln Likely benign ★★ 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/itpr2-p-gln565lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown