PRKCB p.Arg635Cys
c.1903C>T · VCV3938118
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.381 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.65 | unconstrained · MANE · 29 kb · p 8.2e-06 · regional, not allelic |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,890 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000248%
4/1,613,994 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,445 |
| European (non-Finnish) | 0.000169% | 590,005 |
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
- PRKCB
- Protein
- p.Arg635Cys
- Coding
- c.1903C>T
- MANE Select
- NM_002738
- Type
- single nucleotide variant
- Location
- chr16:24214697 (GRCh38)
- Gene constraint
- LOEUF 0.241 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.95 · 8 PDB
- Residue 635
- an α-helix; a modified residue (phosphothreonine; by autocatalysis); the agc-kinase c-terminal domain; the 'disordered' region
Similar variants
- PRKCB c.1395-4A>G Benign ★★ same type
- PRKCB p.Ile174= Benign ★★ same type
- PRKCB p.Lys29= Benign/Likely benign ★★ same type
- PRKCB p.Pro400= Likely benign ★★ same type
- PRKCB p.Ala2Pro Uncertain significance ★ ⚠ same type
- PRKCB p.Ala395Thr Uncertain significance ★ ⚠ same type
- PRKCB p.Ala539Thr Uncertain significance ★ ⚠ same type
- PRKCB p.Ala6Thr 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/prkcb-p-arg635cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown