CDH23 p.Ser166=
c.498C>T · rs765185595 · VCV753671
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
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 -4.7 | GERP -2.9 |
| Overall | ||
| CADD | 5.925 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,868 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00105%
17/1,613,718 alleles · ultra-rare
exomes 17/1,461,378 · genomes 0/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,985 |
| South Asian | 0.00439% | 22,767 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| European (non-Finnish) | 0.00017% | 589,831 |
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
- CDH23
- Protein
- p.Ser166=
- Coding
- c.498C>T
- MANE Select
- NM_022124
- dbSNP
- rs765185595
- Type
- single nucleotide variant
- Location
- chr10:71566810 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 166
- the cadherin 2 domain
Similar variants
- CDH23 p.Ser166fs Pathogenic/Likely pathogenic ★★ same residue
- CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same type
- CDH23 p.Asp127Gly Likely pathogenic ★★★ same type
- CDH23 p.Glu956Lys Pathogenic ★★★ same type
- CDH23 p.Pro240Leu Pathogenic ★★★ same type
- CDH23 c.1515-12G>A Uncertain significance ★★★ same type
- CDH23 p.Ala3190Val Uncertain significance ★★★ same type
- CDH23 p.Arg301Gln Uncertain significance ★★★ same type
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/cdh23-p-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown