CDHR2 p.Pro396=
c.1188G>A · rs147274233 · VCV2656088
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.171%, nfe)
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 -1.1 | GERP -2.7 |
| Overall | ||
| CADD | 6.239 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.171%
European (non-Finnish) · 2,011/1,179,186 alleles
Filtering AF
0.164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.162%
Overall
0.132%
2,126/1,610,468 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.171% | 586 |
| Remaining individualsnot grpmax-eligible | 0.0961% | 1,041 |
| Admixed American | 0.045% | 2,221 |
| African / African-American | 0.0307% | 3,262 |
| Finnishnot grpmax-eligible | 0.00651% | 15,370 |
| East Asian | 0.00223% | 44,866 |
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
- CDHR2
- Protein
- p.Pro396=
- Coding
- c.1188G>A
- MANE Select
- NM_017675
- dbSNP
- rs147274233
- Type
- single nucleotide variant
- Location
- chr5:176576179 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 2 PDB
- Residue 396
- the cadherin 4 domain
Similar variants
- CDHR2 p.Pro396Arg Uncertain significance ★ ⚠ same residue
- CDHR2 p.Pro396Leu Uncertain significance ★ ⚠ same residue
- CDHR2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
- CDHR2 p.Ala121Thr Uncertain significance ★ ⚠ same type
- CDHR2 p.Ala13Val Uncertain significance ★ ⚠ same type
- CDHR2 p.Ala415Thr Uncertain significance ★ ⚠ same type
- CDHR2 p.Ala423Thr Uncertain significance ★ ⚠ same type
- CDHR2 p.Ala512Thr 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/cdhr2-p-pro396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown