PRKCE p.Ser135=
c.405G>A · VCV3783333
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, sas)
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 -3.7 | GERP -4.4 |
| Overall | ||
| CADD | 7.376 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
South Asian · 20/91,088 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00347%
56/1,613,956 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.022% | 4,554 |
| Admixed American | 0.00667% | 15,002 |
| European (non-Finnish) | 0.00254% | 39,332 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| Finnishnot grpmax-eligible | 0.00156% | 64,000 |
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.Ser135=
- Coding
- c.405G>A
- MANE Select
- NM_005400
- Type
- single nucleotide variant
- Location
- chr2:45843056 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.45 · 2 PDB
Similar variants
- PRKCE p.Ala654Thr Benign ★★ same type
- PRKCE p.Lys437= 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
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-ser135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown