CDH23 p.Ser1615=
c.4845G>A · rs542618168 · VCV1343701
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00229%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.61 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.43 | loss · gain 0.41 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP 0.089, phastCons 0.15 |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00229%
East Asian · 1/43,666 alleles
Filtering AF
0.000364%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000263%
Overall
0.000757%
12/1,584,436 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00229% | 43,666 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,356 |
| South Asian | 0.00115% | 87,108 |
| European (non-Finnish) | 0.000773% | 129,394 |
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.Ser1615=
- Coding
- c.4845G>A
- MANE Select
- NM_022124
- dbSNP
- rs542618168
- Type
- single nucleotide variant
- Location
- chr10:71741921 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1615
- the cadherin 15 domain
Similar variants
- CDH23 p.Ser1615Leu Uncertain significance ★ same residue
- CDH23 p.Ser1615Pro Uncertain significance ★ 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
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-ser1615 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown