Is PRKAR1A p.Val253= (c.759C>G) pathogenic?

PRKAR1A p.Val253= (c.759C>G) is classified Likely benign in PRKAR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Absent from gnomAD v4.1; Associated with Carney complex, type 1.

What condition is associated with PRKAR1A p.Val253= (c.759C>G)?

PRKAR1A p.Val253= (c.759C>G) is associated with Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Val253= (c.759C>G) in the general population?

PRKAR1A p.Val253= (c.759C>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.

PRKAR1A p.Val253=

c.759C>G · VCV3643674

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.22	GERP -4.3, phastCons 0.035
Overall
CADD	5.895	PHRED · no single calibrated threshold — expert panels disagree

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.Val253=
Coding: c.759C>G
MANE Select: NM_002734
Type: single nucleotide variant
Location: chr17:68527890 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB

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.Val253Ile Uncertain significance ★★ ⚠ same residue
PRKAR1A p.Val253Ala 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

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-val253 (accessed [today's date]).

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