ITPR3 p.Asp658=
c.1974C>T · rs140399440 · VCV3046673
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0703%, nfe)
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 -0.27 | GERP -3.5, phastCons 0.16 |
| Overall | ||
| CADD | 9.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0703%
European (non-Finnish) · 829/1,180,034 alleles
Filtering AF
0.0662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0646%
Overall
0.054%
872/1,614,218 alleles · ultra-rare
exomes 824/1,461,876 · genomes 48/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0703% | 1,423 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Admixed American | 0.0217% | 4,617 |
| African / African-American | 0.016% | 6,256 |
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
- ITPR3
- Protein
- p.Asp658=
- Coding
- c.1974C>T
- MANE Select
- NM_002224
- dbSNP
- rs140399440
- Type
- single nucleotide variant
- Location
- chr6:33668602 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
Similar variants
- 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
- ITPR3 p.Gly2514Glu 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-asp658 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown