ITPR1 p.Ser2502=
c.7506C>T · rs375227391 · VCV447598
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 -3.8 | GERP -2.9 |
| Overall | ||
| CADD | 2.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,046 alleles
Filtering AF
0.0131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.012%
194/1,613,932 alleles · ultra-rare
exomes 178/1,461,678 · genomes 16/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,023 |
| European (non-Finnish) | 0.0149% | 6,704 |
| African / African-American | 0.00933% | 10,715 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| South Asian | 0.00439% | 22,771 |
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.Ser2502=
- Coding
- c.7506C>T
- MANE Select
- NM_001378452
- dbSNP
- rs375227391
- Type
- single nucleotide variant
- Location
- chr3:4813179 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 2502
- the 'interaction with erp44' region
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-ser2502 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown