ITPR3 p.Val1822=
c.5466C>T · rs769011935 · VCV797127
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -3.9 |
| Overall | ||
| CADD | 0.493 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,856 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000277%
Overall
0.000558%
9/1,613,278 alleles · very rare
exomes 8/1,461,070 · genomes 1/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,428 |
| Admixed American | 0.00167% | 59,952 |
| African / African-American | 0.00133% | 74,912 |
| European (non-Finnish) | 0.000424% | 235,929 |
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
- ITPR3
- Protein
- p.Val1822=
- Coding
- c.5466C>T
- MANE Select
- NM_002224
- dbSNP
- rs769011935
- Type
- single nucleotide variant
- Location
- chr6:33685517 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 1822
- the 'disordered' region
Similar variants
- ITPR3 p.Thr1424Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- ITPR3 p.Ala1352Thr Uncertain significance ★★ ⚠ same type
- ITPR3 p.Arg1085Leu Uncertain significance ★★ ⚠ same type
- ITPR3 p.Arg2659Cys Uncertain significance ★★ ⚠ same type
- ITPR3 p.Asp1968Val Uncertain significance ★★ ⚠ same type
- ITPR3 p.Glu669Asp Uncertain significance ★★ ⚠ same type
- ITPR3 p.Gly1008Trp Uncertain significance ★★ ⚠ same type
- ITPR3 p.Gly2514Glu 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/itpr3-p-val1822 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown