CASR p.Leu730=
c.2190C>G · rs2074933154 · VCV1787419
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Nephrolithiasis/nephrocalcinosis
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 0.44 | GERP -1.1, phastCons 0.99 |
| Overall | ||
| CADD | 7.082 | PHRED · no single calibrated threshold — expert panels disagree |
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
- CASR
- Protein
- p.Leu730=
- Coding
- c.2190C>G
- MANE Select
- NM_000388
- dbSNP
- rs2074933154
- Type
- single nucleotide variant
- Location
- chr3:122284144 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.01 · 31 PDB
- Residue 730
- a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); an α-helix
Similar variants
- CASR p.Leu730Phe Uncertain significance ★ ⚠ same residue
- CASR p.Arg465Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CASR p.Glu767Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CASR p.Ile555Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CASR p.Ala168Ser Uncertain significance ★★ ⚠ same condition
- CASR p.Ala390Asp Uncertain significance ★★ ⚠ same condition
- CASR p.Ala430Ser Uncertain significance ★★ ⚠ same condition
- CASR p.Ala45Glu 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/casr-p-leu730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown