ITPR3 p.Ser1657=
c.4971G>A · rs118044529 · VCV779908
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.11%, eas)
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 -20 | GERP -4.8 |
| Overall | ||
| CADD | 0.847 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.11%
East Asian · 1,842/44,872 alleles
Filtering AF
3.95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.89%
Overall
0.181%
2,924/1,614,044 alleles · low-frequency
exomes 2,637/1,461,782 · genomes 287/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.11% | 24 |
| South Asian | 0.863% | 116 |
| Remaining individualsnot grpmax-eligible | 0.357% | 280 |
| Admixed American | 0.045% | 2,223 |
| Middle Eastern | 0.033% | 3,031 |
| European (non-Finnish) | 0.00356% | 28,095 |
| Finnishnot grpmax-eligible | 0.00156% | 63,990 |
| African / African-American | 0.00133% | 75,008 |
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.Ser1657=
- Coding
- c.4971G>A
- MANE Select
- NM_002224
- dbSNP
- rs118044529
- Type
- single nucleotide variant
- Location
- chr6:33684390 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 1657
- a turn
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-ser1657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown