ITPR2 p.Leu756=
c.2268G>C · rs150957410 · VCV736883
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.417%, afr)
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 -3.5 | GERP -3.8 |
| Overall | ||
| CADD | 2.223 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.417%
African / African-American · 313/75,058 alleles
Filtering AF
0.379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.364%
Overall
0.0247%
399/1,614,224 alleles · rare
exomes 199/1,461,888 · genomes 200/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.417% | 240 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.0533% | 1,876 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,125 |
| South Asian | 0.00329% | 30,363 |
| European (non-Finnish) | 0.0022% | 45,386 |
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
- ITPR2
- Protein
- p.Leu756=
- Coding
- c.2268G>C
- MANE Select
- NM_002223
- dbSNP
- rs150957410
- Type
- single nucleotide variant
- Location
- chr12:26656473 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
Similar variants
- 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
- ITPR2 p.Asn461= 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-leu756 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown