ITPR1 p.Asp828=
c.2484T>C · VCV4682228
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 0.0166%, mid)
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 -0.098 | GERP -1.5, phastCons 0.84 |
| Overall | ||
| CADD | 6.946 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,022 alleles
Filtering AF
0.000127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.3e-05%
Overall
0.000514%
8/1,556,820 alleles · ultra-rare
exomes 5/1,404,620 · genomes 3/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,022 |
| Admixed American | 0.00197% | 50,776 |
| South Asian | 0.00119% | 83,808 |
| European (non-Finnish) | 0.000435% | 229,934 |
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.Asp828=
- Coding
- c.2484T>C
- MANE Select
- NM_001378452
- Type
- single nucleotide variant
- Location
- chr3:4674229 (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-asp828 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown