PRKCB p.Ile174=
c.522T>C · rs116345778 · VCV779163
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.24%, 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 -2.4 | GERP -3.5 |
| Overall | ||
| CADD | 3.792 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.24%
South Asian · 2,036/90,770 alleles
Filtering AF
2.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.13%
Overall
0.355%
5,664/1,597,342 alleles · low-frequency
exomes 4,692/1,446,496 · genomes 972/150,846 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.24% | 45 |
| African / African-American | 1.7% | 59 |
| Middle Eastern | 1.57% | 64 |
| Remaining individualsnot grpmax-eligible | 0.463% | 216 |
| Admixed American | 0.246% | 407 |
| Ashkenazi Jewishnot grpmax-eligible | 0.245% | 408 |
| Amishnot grpmax-eligible | 0.221% | 453 |
| European (non-Finnish) | 0.151% | 661 |
| East Asian | 0.00232% | 43,140 |
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.Ile174=
- Coding
- c.522T>C
- MANE Select
- NM_002738
- dbSNP
- rs116345778
- Type
- single nucleotide variant
- Location
- chr16:24035540 (GRCh38)
- Gene constraint
- LOEUF 0.241 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.95 · 8 PDB
- Residue 174
- the c2 domain; a β-strand
Similar variants
- PRKCB c.1395-4A>G 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
- PRKCB p.Ala6Val 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-ile174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown