ITPR3 p.Pro1581=
c.4743C>T · rs942636 · VCV1293580
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 31%, amr) — too common for a highly-penetrant pathogenic allele
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 0.81 | GERP -0.39, phastCons 0.99 |
| Overall | ||
| CADD | 9.389 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
31%
Admixed American · 17,652/56,974 alleles
Filtering AF
30.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 30.4%
Overall
17.8%
284,214/1,593,846 alleles · common
exomes 255,311/1,441,566 · genomes 28,903/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 31% | 3 |
| Finnishnot grpmax-eligible | 26.8% | 4 |
| South Asian | 21.2% | 5 |
| Amishnot grpmax-eligible | 19% | 5 |
| Middle Eastern | 18.4% | 5 |
| African / African-American | 17.9% | 6 |
| Remaining individualsnot grpmax-eligible | 17% | 6 |
| European (non-Finnish) | 16.8% | 6 |
| Ashkenazi Jewishnot grpmax-eligible | 15.4% | 7 |
| East Asian | 11.7% | 9 |
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.Pro1581=
- Coding
- c.4743C>T
- MANE Select
- NM_002224
- dbSNP
- rs942636
- Type
- single nucleotide variant
- Location
- chr6:33683352 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 1581
- an α-helix
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-pro1581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown