CDH23 p.Arg1594=
c.4782C>T · rs756336099 · VCV287383
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0487%, sas)
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 -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.067 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0487%
South Asian · 44/90,412 alleles
Filtering AF
0.0372%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0332%
Overall
0.00472%
76/1,610,894 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0487% | 2,055 |
| Middle Eastern | 0.0164% | 6,080 |
| African / African-American | 0.00401% | 24,969 |
| Admixed American | 0.00335% | 29,850 |
| European (non-Finnish) | 0.00212% | 47,155 |
| Finnishnot grpmax-eligible | 0.00158% | 63,350 |
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.Arg1594=
- Coding
- c.4782C>T
- MANE Select
- NM_022124
- dbSNP
- rs756336099
- Type
- single nucleotide variant
- Location
- chr10:71741858 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1594
- the cadherin 15 domain
Similar variants
- CDH23 p.Arg1594Cys Uncertain significance ★★ ⚠ same residue
- CDH23 p.Arg1594His Uncertain significance ★★ same residue
- CDH23 p.Arg1594Leu 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
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-arg1594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown