Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.92%, afr)
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 3.9 | phastCons 1 |
| Overall | ||
| CADD | 12.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.92%
African / African-American · 1,442/75,040 alleles
Filtering AF
1.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.81%
Overall
0.0978%
1,578/1,614,162 alleles · low-frequency
exomes 794/1,461,858 · genomes 784/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.92% | 52 |
| Remaining individualsnot grpmax-eligible | 0.096% | 1,042 |
| Admixed American | 0.0766% | 1,305 |
| Middle Eastern | 0.066% | 1,516 |
| South Asian | 0.00549% | 18,216 |
| European (non-Finnish) | 0.00178% | 56,192 |
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
- PRKACA
- Protein
- p.Arg281=
- Coding
- c.843C>G
- MANE Select
- NM_002730
- dbSNP
- rs3729858
- Type
- single nucleotide variant
- Location
- chr19:14093715 (GRCh38)
- Gene constraint
- LOEUF 0.338 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 95.92 · 54 PDB
- Residue 281
- the protein kinase domain
Similar variants
- PRKACA p.Gly137Arg Pathogenic/Likely pathogenic ★★ same type
- PRKACA p.Arg271Trp Uncertain significance ★★ ⚠ same type
- PRKACA p.Asn341Ser Uncertain significance ★★ ⚠ same type
- PRKACA p.Gly67Arg Uncertain significance ★★ ⚠ same type
- PRKACA c.109-6C>T Benign/Likely benign ★★ same type
- PRKACA c.47-418C>T Benign/Likely benign ★★ same type
- PRKACA p.Gly127= Benign ★★ same type
- PRKACA p.Phe55= Likely benign ★★ 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/prkaca-p-arg281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown