PRKCG p.Pro508=
c.1524C>A · rs115736276 · VCV194377
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.247%, afr)
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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 0.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
African / African-American · 185/75,040 alleles
Filtering AF
0.217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.206%
Overall
0.0121%
195/1,614,208 alleles · rare
exomes 94/1,461,884 · genomes 101/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.247% | 406 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.00333% | 30,014 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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
- PRKCG
- Protein
- p.Pro508=
- Coding
- c.1524C>A
- MANE Select
- NM_002739
- dbSNP
- rs115736276
- Type
- single nucleotide variant
- Location
- chr19:53900698 (GRCh38)
- Gene constraint
- LOEUF 0.476 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 82.32 · 2 PDB
- Residue 508
- the protein kinase domain
Similar variants
- PRKCG p.Asn642Lys Likely pathogenic ★★ same type
- PRKCG p.Gln127Arg Pathogenic ★★ same type
- PRKCG p.Gln127Lys Likely pathogenic ★★ same type
- PRKCG p.Gly63Val Likely pathogenic ★★ same type
- PRKCG p.His101Tyr Pathogenic/Likely pathogenic ★★ same type
- PRKCG p.His74Asn Likely pathogenic ★★ same type
- PRKCG p.His74Tyr Likely pathogenic ★★ same type
- PRKCG p.Leu120Phe 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/prkcg-p-pro508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown