PCDH19 p.Pro344=
c.1032G>C · rs1429555639 · VCV1131964
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000335%, nfe)
Conditions
1
developmental and epileptic encephalopathy, 9
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 -11 | GERP -5.5 |
| Overall | ||
| CADD | 0.495 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000335%
European (non-Finnish) · 3/895,131 alleles
Filtering AF
8.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000248%
3/1,209,995 alleles · very rare
exomes 2/1,097,307 · genomes 1/112,688 · joint denominator
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
- PCDH19
- Protein
- p.Pro344=
- Coding
- c.1032G>C
- MANE Select
- NM_001184880
- dbSNP
- rs1429555639
- Type
- single nucleotide variant
- Location
- chrX:100407566 (GRCh38)
- Structure
- AlphaFold pLDDT 68.50 · 1 PDB
- Residue 344
- a UniProt-annotated variant site (in dee9); the cadherin 3 domain
Similar variants
- PCDH19 p.Pro344Arg Pathogenic ★★ same residue
- PCDH19 p.Pro344Gln Likely pathogenic ★★ same residue
- PCDH19 p.Pro344Leu Pathogenic/Likely pathogenic ★★ same residue
- PCDH19 p.Pro344Ala Likely pathogenic ★ same residue
- PCDH19 p.Pro344Ser Likely pathogenic ★ same residue
- PCDH19 c.2675+1G>T Pathogenic/Likely pathogenic ★★ same condition
- PCDH19 c.2675+2T>C Pathogenic ★★ same condition
- PCDH19 p.Arg198Leu Pathogenic/Likely pathogenic ★★ same condition
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/pcdh19-p-pro344 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown