CDHR4 p.Leu503=
c.1507T>C · VCV3489099
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0275%, amr)
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 0.68 | GERP -2.8, phastCons 0.96 |
| Overall | ||
| CADD | 5.094 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0275%
Admixed American · 14/50,988 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0133%
Overall
0.00264%
41/1,551,604 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0275% | 3,642 |
| African / African-American | 0.00411% | 24,349 |
| European (non-Finnish) | 0.00201% | 49,869 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,094 |
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
- CDHR4
- Protein
- p.Leu503=
- Coding
- c.1507T>C
- MANE Select
- NM_001007540
- Type
- single nucleotide variant
- Location
- chr3:49793699 (GRCh38)
- Gene constraint
- LOEUF 1.174 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.90
- Residue 503
- the cadherin 3 domain
Similar variants
- CDHR4 p.Ala12Val Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala149Val Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala302Val Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala310Pro Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala318Asp Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala341Pro Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala385Gly Uncertain significance ★ ⚠ same type
- CDHR4 p.Ala456Pro 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/cdhr4-p-leu503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown