PRKCA p.Pro221=
c.663G>A · VCV4144398
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00483%, nfe)
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 -0.64 | GERP -2.7, phastCons 0.011 |
| Overall | ||
| CADD | 11.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00483%
European (non-Finnish) · 57/1,179,962 alleles
Filtering AF
0.00378%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00345%
Overall
0.00378%
61/1,613,850 alleles · very rare
exomes 58/1,461,760 · genomes 3/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00483% | 20,701 |
| East Asian | 0.00223% | 44,896 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00134% | 74,874 |
| South Asian | 0.0011% | 91,076 |
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
- PRKCA
- Protein
- p.Pro221=
- Coding
- c.663G>A
- MANE Select
- NM_002737
- Type
- single nucleotide variant
- Location
- chr17:66687244 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.90 · 6 PDB
- Residue 221
- the c2 domain
Similar variants
- PRKCA p.Pro221Leu Uncertain significance ★ ⚠ same residue
- PRKCA p.Asn279= Benign ★★ same type
- PRKCA p.Gly129= Benign ★★ same type
- PRKCA p.Leu277= Benign ★★ same type
- PRKCA p.Ala356Thr Uncertain significance ★ ⚠ same type
- PRKCA p.Arg324Lys Uncertain significance ★ ⚠ same type
- PRKCA p.Arg333Gln Uncertain significance ★ ⚠ same type
- PRKCA p.Arg496Gly 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/prkca-p-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown