CDH23 p.Pro1973=
c.5919C>T · rs752519912 · VCV227230
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0337%, mid)
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 -7.7 | GERP -3.4 |
| Overall | ||
| CADD | 2.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0337%
Middle Eastern · 2/5,934 alleles
Filtering AF
0.00593%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00246%
Overall
0.00326%
50/1,533,630 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0337% | 2,967 |
| Remaining individualsnot grpmax-eligible | 0.0117% | 8,543 |
| East Asian | 0.009% | 11,113 |
| Admixed American | 0.00667% | 14,983 |
| African / African-American | 0.00545% | 18,359 |
| South Asian | 0.00447% | 22,360 |
| European (non-Finnish) | 0.00226% | 44,276 |
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.Pro1973=
- Coding
- c.5919C>T
- MANE Select
- NM_022124
- dbSNP
- rs752519912
- Type
- single nucleotide variant
- Location
- chr10:71789038 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1973
- the cadherin 19 domain
Similar variants
- CDH23 p.Pro1973fs 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-pro1973 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown