PRKCE p.Lys437=
c.1311G>A · rs56005919 · VCV771697
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.832%, 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 1.3 | GERP -5, phastCons 1 |
| Overall | ||
| CADD | 5.466 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.832%
European (non-Finnish) · 9,815/1,179,888 alleles
Filtering AF
0.818%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.812%
Overall
0.662%
10,582/1,599,602 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.832% | 120 |
| Remaining individualsnot grpmax-eligible | 0.524% | 191 |
| Finnishnot grpmax-eligible | 0.269% | 371 |
| Admixed American | 0.255% | 392 |
| African / African-American | 0.129% | 773 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0709% | 1,410 |
| South Asian | 0.0351% | 2,846 |
| Middle Eastern | 0.033% | 3,030 |
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
- PRKCE
- Protein
- p.Lys437=
- Coding
- c.1311G>A
- MANE Select
- NM_005400
- dbSNP
- rs56005919
- Type
- single nucleotide variant
- Location
- chr2:46010391 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.45 · 2 PDB
- Residue 437
- a binding site; the protein kinase domain
Similar variants
- PRKCE p.Ala654Thr Benign ★★ same type
- PRKCE p.Thr455= Benign ★★ same type
- PRKCE p.Glu328Gln Likely pathogenic ★ ⚠ same type
- PRKCE p.Glu599Lys Pathogenic ★ same type
- PRKCE p.Arg150Cys Uncertain significance ★ ⚠ same type
- PRKCE p.Arg150His Uncertain significance ★ same type
- PRKCE p.Arg152Gln Uncertain significance ★ ⚠ same type
- PRKCE p.Arg282His 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/prkce-p-lys437 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown