Is PRKAR1A p.Pro119= (c.357A>G) pathogenic?

PRKAR1A p.Pro119= (c.357A>G) is classified Likely benign in PRKAR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Very rare (popmax 0.00329%, sas); Associated with Carney complex, type 1.

What condition is associated with PRKAR1A p.Pro119= (c.357A>G)?

PRKAR1A p.Pro119= (c.357A>G) is associated with Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Pro119= (c.357A>G) in the general population?

PRKAR1A p.Pro119= (c.357A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Carney complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PRKAR1A p.Pro119=

c.357A>G · rs779193269 · VCV1112269

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Carney complex, type 1

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 -1.4	GERP -3.7
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,050 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,122 alleles · very rare exomes 5/1,460,742 · genomes 0/152,380 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,350
East Asian	0.00223%	44,876
European (non-Finnish)	8.48e-05%	1,179,632

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: PRKAR1A
Protein: p.Pro119=
Coding: c.357A>G
MANE Select: NM_002734
dbSNP: rs779193269
Type: single nucleotide variant
Location: chr17:68523733 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 119: the 'dimerization and phosphorylation' region

Full PRKAR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Carney complex, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carney complex (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PRKAR1A p.Pro119Thr Uncertain significance ★★ ⚠ same residue
PRKAR1A c.502+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A c.549+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A c.891+1G>A Likely pathogenic ★★ same condition
PRKAR1A c.891+3A>G Likely pathogenic ★★ same condition
PRKAR1A p.Arg16Ter Pathogenic ★★ same condition
PRKAR1A p.Arg228Ter Pathogenic ★★ same condition
PRKAR1A p.Arg335Cys Pathogenic/Likely pathogenic ★★ same condition

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/prkar1a-p-pro119 (accessed [today's date]).

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