CDHR1 p.Arg280=
c.838C>A · rs191858417 · VCV1673666
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.22 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 3.8, phastCons 0.97 |
| Overall | ||
| CADD | 8.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,880 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00916%
Overall
0.00124%
20/1,613,260 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0223% | 4,488 |
| Finnishnot grpmax-eligible | 0.00469% | 21,345 |
| South Asian | 0.0022% | 45,537 |
| European (non-Finnish) | 0.000424% | 235,868 |
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
- CDHR1
- Protein
- p.Arg280=
- Coding
- c.838C>A
- MANE Select
- NM_033100
- dbSNP
- rs191858417
- Type
- single nucleotide variant
- Location
- chr10:84204581 (GRCh38)
- Gene constraint
- LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 78.79
- Residue 280
- the cadherin 3 domain
Similar variants
- CDHR1 p.Arg280Ter Pathogenic ★ same residue
- CDHR1 p.Arg280Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDHR1 c.1168-1G>C Pathogenic/Likely pathogenic ★★ same type
- CDHR1 c.1321-1G>A Likely pathogenic ★★ same type
- CDHR1 c.1485+2T>C Pathogenic ★★ same type
- CDHR1 c.1485+2T>G Pathogenic ★★ same type
- CDHR1 c.1554-2A>C Pathogenic/Likely pathogenic ★★ same type
- CDHR1 c.297+1G>T Pathogenic ★★ 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/cdhr1-p-arg280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown