PCDH12 p.Pro475=
c.1425C>T · rs367840034 · VCV1995800
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.4 | GERP -5.7, phastCons 0.96 |
| Overall | ||
| CADD | 6.351 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/74,942 alleles
Filtering AF
0.00921%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00721%
Overall
0.000929%
15/1,614,130 alleles · ultra-rare
exomes 12/1,461,894 · genomes 3/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,245 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| European (non-Finnish) | 8.47e-05% | 1,180,058 |
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
- PCDH12
- Protein
- p.Pro475=
- Coding
- c.1425C>T
- MANE Select
- NM_016580
- dbSNP
- rs367840034
- Type
- single nucleotide variant
- Location
- chr5:141956427 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22
- Residue 475
- the cadherin 5 domain
Similar variants
- PCDH12 p.Arg151Ter Pathogenic ★★ same type
- PCDH12 p.Arg308Ter Pathogenic/Likely pathogenic ★★ same type
- PCDH12 p.Arg839Ter Pathogenic ★★ same type
- PCDH12 p.Ala1132Thr Uncertain significance ★★ ⚠ same type
- PCDH12 p.Ala148Thr Uncertain significance ★★ ⚠ same type
- PCDH12 p.Ala802Val Uncertain significance ★★ ⚠ same type
- PCDH12 p.Ala905Thr Uncertain significance ★★ ⚠ same type
- PCDH12 p.Arg1049Gln 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/pcdh12-p-pro475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown