CASR p.Ser166=
c.498T>C · rs2473225010 · VCV3231577
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00266%, afr)
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 -0.17 | GERP -0.83, phastCons 0.37 |
| Overall | ||
| CADD | 7.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00266%
African / African-American · 2/75,050 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000137%
2/1,461,764 alleles · very rare
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
- CASR
- Protein
- p.Ser166=
- Coding
- c.498T>C
- MANE Select
- NM_000388
- dbSNP
- rs2473225010
- Type
- single nucleotide variant
- Location
- chr3:122261533 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.01 · 31 PDB
- Residue 166
- a UniProt-annotated variant site (in hhc1); the 'ligand-binding 1 (lb1)' region; a β-strand
Similar variants
- CASR p.Ser166Asn Uncertain significance ★★ ⚠ same residue
- CASR p.Ser166Arg Uncertain significance ★ ⚠ same residue
- CASR p.Ser166Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- CASR p.Ser166Ile 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
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-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown