PCDH19 p.Ser67=
c.201G>A · rs202078154 · VCV1355184
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, afr)
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 -4.3 | GERP -5.5 |
| Overall | ||
| CADD | 3.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
African / African-American · 6/57,051 alleles
Filtering AF
0.00457%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00307%
Overall
0.000663%
8/1,206,319 alleles · ultra-rare
exomes 7/1,095,103 · genomes 1/111,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0105% | 9,509 |
| East Asian | 0.00297% | 33,653 |
| European (non-Finnish) | 0.000112% | 894,158 |
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.Ser67=
- Coding
- c.201G>A
- MANE Select
- NM_001184880
- dbSNP
- rs202078154
- Type
- single nucleotide variant
- Location
- chrX:100408397 (GRCh38)
- Structure
- AlphaFold pLDDT 68.50 · 1 PDB
- Residue 67
- a β-strand; the cadherin 1 domain
Similar variants
- PCDH19 p.Ser67Ter Pathogenic ★★ same residue
- PCDH19 p.Ser67Trp Uncertain significance ★ ⚠ 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
- PCDH19 p.Arg207Ter Pathogenic ★★ same condition
- PCDH19 p.Arg372Trp Pathogenic/Likely pathogenic ★★ same condition
- PCDH19 p.Arg395Ter 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-ser67 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown