ITPR3 p.Asp1395=
c.4185C>T · rs41271253 · VCV770551
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele
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 -14 | GERP -4.8 |
| Overall | ||
| CADD | 5.519 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.9%
African / African-American · 4,428/75,022 alleles
Filtering AF
5.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.7%
Overall
0.456%
7,362/1,613,558 alleles · common
exomes 4,540/1,461,296 · genomes 2,822/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.9% | 17 |
| Middle Eastern | 0.792% | 126 |
| Remaining individualsnot grpmax-eligible | 0.723% | 138 |
| Admixed American | 0.7% | 143 |
| South Asian | 0.187% | 536 |
| European (non-Finnish) | 0.15% | 668 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0811% | 1,234 |
| East Asian | 0.0758% | 1,320 |
| Finnishnot grpmax-eligible | 0.0315% | 3,173 |
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.Asp1395=
- Coding
- c.4185C>T
- MANE Select
- NM_002224
- dbSNP
- rs41271253
- Type
- single nucleotide variant
- Location
- chr6:33680094 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 1395
- an α-helix
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-asp1395 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown