ITPR3 p.Asp742=
c.2226C>T · rs2229633 · VCV3052627
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.621%, afr)
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 1.4 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 10.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.621%
African / African-American · 466/75,048 alleles
Filtering AF
0.574%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.556%
Overall
0.0521%
841/1,614,120 alleles · rare
exomes 612/1,461,798 · genomes 229/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.621% | 161 |
| Admixed American | 0.0666% | 1,501 |
| Remaining individualsnot grpmax-eligible | 0.0496% | 2,017 |
| Middle Eastern | 0.0495% | 2,021 |
| European (non-Finnish) | 0.0254% | 3,933 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
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
- ITPR3
- Protein
- p.Asp742=
- Coding
- c.2226C>T
- MANE Select
- NM_002224
- dbSNP
- rs2229633
- Type
- single nucleotide variant
- Location
- chr6:33670361 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 742
- a turn; a UniProt-annotated variant site (in)
Similar variants
- ITPR3 p.Asp742Glu Benign/Likely benign ★★ ⚠ same residue
- ITPR3 p.Thr1424Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- ITPR3 p.Ala1352Thr Uncertain significance ★★ ⚠ same type
- ITPR3 p.Arg1085Leu Uncertain significance ★★ ⚠ same type
- ITPR3 p.Arg2659Cys Uncertain significance ★★ ⚠ same type
- ITPR3 p.Asp1968Val Uncertain significance ★★ ⚠ same type
- ITPR3 p.Glu669Asp Uncertain significance ★★ ⚠ same type
- ITPR3 p.Gly1008Trp Uncertain significance ★★ ⚠ 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/itpr3-p-asp742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown