ITPR3 p.Ser2042=
c.6126G>A · rs778571725 · VCV2656501
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 |
|---|---|---|
| Pangolin | Δ0.21 | gain · loss 0.06 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4.8 |
| Overall | ||
| CADD | 0.512 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,982 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00143%
23/1,613,708 alleles · very rare
exomes 22/1,461,618 · genomes 1/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,991 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| Finnishnot grpmax-eligible | 0.00312% | 32,001 |
| African / African-American | 0.00267% | 37,436 |
| European (non-Finnish) | 0.00127% | 78,657 |
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.Ser2042=
- Coding
- c.6126G>A
- MANE Select
- NM_002224
- dbSNP
- rs778571725
- Type
- single nucleotide variant
- Location
- chr6:33687276 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.04 · 24 PDB
- Residue 2042
- a β-strand
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-ser2042 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown