ITPR1 p.Arg511Lys
c.1532G>A · VCV4961032
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9889 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
AlphaMissense, REVEL · SaProt no call
Conditions
1
ITPR1-related disorders
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9889 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.817 | moderately pathogenic-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 18 kb · p 1.3e-16 · regional, not allelic |
| Overall | ||
| CADD | 26.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
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.Arg511Lys
- Coding
- c.1532G>A
- MANE Select
- NM_001378452
- Type
- single nucleotide variant
- Location
- chr3:4663184 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 511
- a binding site
Disease context
ITPR1-related disorders
Similar variants
- ITPR1 p.Arg511Gly Likely pathogenic ★★ same residue
- ITPR1 p.Arg511Ser Likely pathogenic ★★ same residue
- ITPR1 c.1252-1G>C Pathogenic/Likely pathogenic ★★ same condition
- ITPR1 p.Glu2109Lys Pathogenic/Likely pathogenic ★★ same condition
- ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
- ITPR1 p.Ile2598Thr Pathogenic/Likely pathogenic ★★ same condition
- ITPR1 p.Val1445Met Likely pathogenic ★★ same condition
- ITPR1 p.Arg1216Trp 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-arg511lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown