PRKACA p.Leu173=
c.519G>T · VCV4941155
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, nfe)
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 0.19 | phastCons 0.77 |
| Overall | ||
| CADD | 4.952 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
European (non-Finnish) · 13/1,180,030 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000889%
13/1,461,882 alleles · very rare
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.Leu173=
- Coding
- c.519G>T
- MANE Select
- NM_002730
- Type
- single nucleotide variant
- Location
- chr19:14097791 (GRCh38)
- Gene constraint
- LOEUF 0.338 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 95.92 · 54 PDB
- Residue 173
- the protein kinase domain; a β-strand
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.Arg281= Benign ★★ same type
- PRKACA p.Gly127= 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-leu173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown