ITPR1 p.Pro2272=
c.6816C>T · rs139021152 · VCV2977319
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00447%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.9 | GERP -5.3 |
| Overall | ||
| CADD | 4.196 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00447%
East Asian · 2/44,760 alleles
Filtering AF
0.000741%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000277%
Overall
0.000621%
10/1,609,742 alleles · very rare
exomes 7/1,457,408 · genomes 3/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00447% | 22,380 |
| Admixed American | 0.00167% | 59,702 |
| Finnishnot grpmax-eligible | 0.00156% | 63,948 |
| European (non-Finnish) | 0.00051% | 196,228 |
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
- ITPR1
- Protein
- p.Pro2272=
- Coding
- c.6816C>T
- MANE Select
- NM_001378452
- dbSNP
- rs139021152
- Type
- single nucleotide variant
- Location
- chr3:4795072 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Similar variants
- 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
- ITPR1 p.Arg511Gly 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-pro2272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown