Is PRKAR1A p.Pro353Arg (c.1058C>G) pathogenic?

PRKAR1A p.Pro353Arg (c.1058C>G) is classified Uncertain significance in PRKAR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.2595); Absent from gnomAD v4.1; Associated with Carney complex, type 1.

What condition is associated with PRKAR1A p.Pro353Arg (c.1058C>G)?

PRKAR1A p.Pro353Arg (c.1058C>G) is associated with Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Pro353Arg (c.1058C>G) in the general population?

PRKAR1A p.Pro353Arg (c.1058C>G) is absent from gnomAD v4.1 (gnomAD).

How is Carney complex inherited?

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

What do computational predictors say about PRKAR1A p.Pro353Arg (c.1058C>G)?

AlphaMissense predicts likely benign (score 0.2595) — an in-silico prediction, not a clinical call.

PRKAR1A p.Pro353Arg

c.1058C>G · VCV3720820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2595 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Carney complex, type 1

Computational evidence

Protein change
AlphaMissense	0.2595	likely benign
REVEL	0.419	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.2, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 127 bp · p 0.00016 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKAR1A
Protein: p.Pro353Arg
Coding: c.1058C>G
MANE Select: NM_002734
Type: single nucleotide variant
Location: chr17:68530361 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 353: an α-helix

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.Pro353Thr 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-pro353arg (accessed [today's date]).

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