CASR p.Cys765fs
c.2292del · VCV4682112
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CASR
- Protein
- p.Cys765fs
- Coding
- c.2292del
- MANE Select
- NM_000388
- Type
- Deletion
- Location
- chr3:122284246 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.01 · 31 PDB
- Residue 765
- a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); a β-strand
Disease context
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia
Similar variants
- CASR p.Cys765_Leu770delinsTrpAlaIleIlePhe Likely pathogenic ★ same residue
- CASR p.Cys765= Likely benign ★★ same residue
- CASR p.Ala826fs Likely pathogenic ★ same condition
- CASR p.Val513fs Likely pathogenic ★ same condition
- CASR p.Val9fs Pathogenic ★ same condition
- CASR p.Cys765Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- CASR p.Cys765Trp Uncertain significance ★ ⚠ same residue
- CASR p.Arg220Trp Pathogenic/Likely pathogenic ★★ 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-cys765fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown