Is PRKACA p.Leu50= (c.150C>T) pathogenic?

PRKACA p.Leu50= (c.150C>T) is classified Likely benign in PRKACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-06). Ultra-rare (popmax 0.0736%, sas); Associated with PRKACA-related disorder.

What condition is associated with PRKACA p.Leu50= (c.150C>T)?

PRKACA p.Leu50= (c.150C>T) is associated with PRKACA-related disorder (ClinVar).

How common is PRKACA p.Leu50= (c.150C>T) in the general population?

PRKACA p.Leu50= (c.150C>T) is ultra-rare (popmax 0.0736%, sas) (gnomAD).

PRKACA p.Leu50=

c.150C>T · rs775474906 · VCV3049005

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, sas)

Conditions

PRKACA-related disorder

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 -5.4
Overall
CADD	3.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0736% South Asian · 67/91,086 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0096% 155/1,614,190 alleles · ultra-rare exomes 151/1,461,878 · genomes 4/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0736%	1,359
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.015%	6,670
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
European (non-Finnish)	0.00492%	20,345

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.Leu50=
Coding: c.150C>T
MANE Select: NM_002730
dbSNP: rs775474906
Type: single nucleotide variant
Location: chr19:14106847 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.92 · 54 PDB
Residue 50: the protein kinase domain; a β-strand; a binding site

Full PRKACA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PRKACA-related disorder

Similar variants

PRKACA p.Thr66Ser Uncertain significance ★ ⚠ same condition
PRKACA p.Gly126Ser Uncertain significance ⚠ same condition
PRKACA c.46+10C>T Likely benign same condition
PRKACA c.46+3338G>A Likely benign same condition
PRKACA c.47-332G>A Benign same condition
PRKACA p.Ile251= Likely benign same condition
PRKACA p.Pro244= Likely benign same condition
PRKACA p.Gly137Arg Pathogenic/Likely pathogenic ★★ 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-leu50 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown