CDH23 p.Pro3059=
c.9177G>A · rs371609236 · VCV46070
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0468%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.4 |
| Overall | ||
| CADD | 5.586 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0468%
East Asian · 21/44,872 alleles
Filtering AF
0.0313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0263%
Overall
0.00446%
72/1,613,966 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0468% | 2,137 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,811 |
| European (non-Finnish) | 0.00331% | 30,254 |
| South Asian | 0.00329% | 30,361 |
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.Pro3059=
- Coding
- c.9177G>A
- MANE Select
- NM_022124
- dbSNP
- rs371609236
- Type
- single nucleotide variant
- Location
- chr10:71811414 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3059
- a UniProt-annotated variant site (in dfnb12)
Similar variants
- CDH23 p.Pro3059Leu Uncertain significance ★★ same residue
- CDH23 p.Pro3059Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDH23 p.Pro3059fs 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
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-pro3059 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown