CDHR5 p.Pro742=
c.2226G>A · VCV4224137
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0182%, mid)
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 -7.5 | GERP -3 |
| Overall | ||
| CADD | 1.844 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0182%
Middle Eastern · 1/5,490 alleles
Filtering AF
0.00246%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00155%
Overall
0.00179%
27/1,511,678 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0182% | 5,490 |
| East Asian | 0.00728% | 13,745 |
| South Asian | 0.00635% | 15,742 |
| Admixed American | 0.00222% | 44,960 |
| Remaining individualsnot grpmax-eligible | 0.00171% | 58,546 |
| European (non-Finnish) | 0.00141% | 70,907 |
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
- CDHR5
- Protein
- p.Pro742=
- Coding
- c.2226G>A
- MANE Select
- NM_021924
- Type
- single nucleotide variant
- Location
- chr11:617663 (GRCh38)
- Gene constraint
- LOEUF 1.479 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.84 · 1 PDB
- Residue 742
- the 'mediates interaction with ush1c and myo7b and is required for proper localization to microvilli tips and function in microvilli organization' region; the 'disordered' region
Similar variants
- CDHR5 p.Arg182His Benign ★★ same type
- CDHR5 p.Gly298= Benign ★★ same type
- CDHR5 p.Ala151Pro Uncertain significance ★ ⚠ same type
- CDHR5 p.Ala171Thr Uncertain significance ★ ⚠ same type
- CDHR5 p.Ala230Thr Uncertain significance ★ ⚠ same type
- CDHR5 p.Ala347Val Uncertain significance ★ ⚠ same type
- CDHR5 p.Ala364Val Uncertain significance ★ ⚠ same type
- CDHR5 p.Ala369Val 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/cdhr5-p-pro742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown