CDH23 p.Gly540=
c.1620C>T · rs374231594 · VCV45878
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.126%, 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 -2.9 |
| Overall | ||
| CADD | 0.242 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.126%
South Asian · 114/90,134 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.1%
Overall
0.0101%
163/1,611,194 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.126% | 791 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,160 |
| Middle Eastern | 0.0164% | 6,080 |
| African / African-American | 0.00267% | 37,421 |
| European (non-Finnish) | 0.00254% | 39,304 |
| Finnishnot grpmax-eligible | 0.00157% | 63,736 |
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.Gly540=
- Coding
- c.1620C>T
- MANE Select
- NM_022124
- dbSNP
- rs374231594
- Type
- single nucleotide variant
- Location
- chr10:71677561 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 540
- the cadherin 5 domain
Similar variants
- CDH23 p.Gly540Ser 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
- 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-gly540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown