PRKACA p.Pro237=
c.711G>A · rs137911238 · VCV755149
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | |
| Overall | ||
| CADD | 1.847 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
European (non-Finnish) · 389/1,180,040 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0292%
Overall
0.0251%
405/1,613,950 alleles · ultra-rare
exomes 374/1,461,820 · genomes 31/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.033% | 3,034 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| East Asian | 0.00891% | 11,223 |
| African / African-American | 0.00267% | 37,445 |
| South Asian | 0.0022% | 45,546 |
| Admixed American | 0.00167% | 59,998 |
| Finnishnot grpmax-eligible | 0.00156% | 63,956 |
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.Pro237=
- Coding
- c.711G>A
- MANE Select
- NM_002730
- dbSNP
- rs137911238
- Type
- single nucleotide variant
- Location
- chr19:14097415 (GRCh38)
- Gene constraint
- LOEUF 0.338 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 95.92 · 54 PDB
- Residue 237
- the protein kinase domain
Similar variants
- PRKACA p.Pro237Leu Uncertain significance ★ ⚠ same residue
- 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.Arg281= 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-pro237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown