ITPR1 p.Cys61Arg
c.181T>C · VCV4858514
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.951 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.951 | likely pathogenic |
|---|---|---|
| REVEL | 0.937 | strongly pathogenic-leaning |
| SaProt | LLR -9.65 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.57 | unconstrained · MANE · 129 kb · p 1.8e-14 · regional, not allelic |
| Overall | ||
| CADD | 28.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ITPR1
- Protein
- p.Cys61Arg
- Coding
- c.181T>C
- MANE Select
- NM_001378452
- Type
- single nucleotide variant
- Location
- chr3:4627780 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Similar variants
- ITPR1 p.Cys61Ser Uncertain significance ★★ ⚠ same residue
- ITPR1 p.Leu605Phe Likely pathogenic ★★ same condition
- ITPR1 p.Thr2434Ile Likely pathogenic ★★ same condition
- ITPR1 c.1554+4G>A Uncertain significance ★★ same condition
- ITPR1 c.3564+5G>T Uncertain significance ★★ same condition
- ITPR1 p.Ala1222Thr Uncertain significance ★★ ⚠ same condition
- ITPR1 p.Ala1222Val Uncertain significance ★★ same condition
- ITPR1 p.Ala1480Thr Uncertain significance ★★ same condition
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/itpr1-p-cys61arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown