CDH23 p.Arg3020His
c.9059G>A · rs767052814 · VCV1479916
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0838 | likely benign |
|---|---|---|
| REVEL | 0.07 | moderately benign-leaning |
| ⇒ AlphaMissense and REVEL both call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 0.63, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic |
| Overall | ||
| CADD | 25.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0234% | 4,267 |
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,227 |
| African / African-American | 0.00267% | 37,450 |
| East Asian | 0.00223% | 44,878 |
| European (non-Finnish) | 0.00119% | 84,271 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg3020His
- Coding
- c.9059G>A
- MANE Select
- NM_022124
- dbSNP
- rs767052814
- Type
- single nucleotide variant
- Location
- chr10:71810551 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- CDH23 p.Arg3020Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDH23 p.Arg3020del 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-arg3020his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown