PCDH15 p.Pro591=
c.1773T>C · rs1178375441 · VCV1117178
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 0.25 | GERP -5.3, phastCons 0.54 |
| Overall | ||
| CADD | 5.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,082 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00118%
19/1,613,830 alleles · very rare
exomes 14/1,461,538 · genomes 5/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,361 |
| European (non-Finnish) | 0.00136% | 73,739 |
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
- PCDH15
- Protein
- p.Pro591=
- Coding
- c.1773T>C
- MANE Select
- NM_001384140
- dbSNP
- rs1178375441
- Type
- single nucleotide variant
- Location
- chr10:54153111 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 66.05 · 8 PDB
- Residue 591
- a turn; the cadherin 5 domain
Similar variants
- PCDH15 p.Pro591Ala Uncertain significance ★ ⚠ same residue
- PCDH15 p.Pro591fs Likely pathogenic same residue
- PCDH15 c.1305+2T>A Likely pathogenic ★★ same type
- PCDH15 c.1306-1G>T Likely pathogenic ★★ same type
- PCDH15 c.1306-2A>G Likely pathogenic ★★ same type
- PCDH15 c.1440+2T>C Likely pathogenic ★★ same type
- PCDH15 c.1441-2A>C Likely pathogenic ★★ same type
- PCDH15 c.158-2A>T Pathogenic/Likely 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/pcdh15-p-pro591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown