ITPR1 p.His93=
c.279C>T · rs371299264 · VCV388806
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 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 -6.4 | GERP -4.3 |
| Overall | ||
| CADD | 0.928 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,044 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00243%
Overall
0.00125%
20/1,598,132 alleles · ultra-rare
exomes 18/1,445,950 · genomes 2/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,022 |
| African / African-American | 0.00402% | 24,860 |
| Remaining individualsnot grpmax-eligible | 0.00324% | 30,906 |
| South Asian | 0.00111% | 90,106 |
| European (non-Finnish) | 0.00103% | 97,256 |
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.His93=
- Coding
- c.279C>T
- MANE Select
- NM_001378452
- dbSNP
- rs371299264
- Type
- single nucleotide variant
- Location
- chr3:4627878 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Similar variants
- ITPR1 p.His93Arg Uncertain significance ★ same residue
- ITPR1 p.His93Gln Uncertain significance ★ same residue
- 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
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-his93 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown