Is PRKAR1A p.Ala41= (c.123T>G) pathogenic?

PRKAR1A p.Ala41= (c.123T>G) is classified Likely benign in PRKAR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-04). Very rare (popmax 0.000169%, nfe); Associated with Carney complex, type 1.

What condition is associated with PRKAR1A p.Ala41= (c.123T>G)?

PRKAR1A p.Ala41= (c.123T>G) is associated with Carney complex, type 1, hereditary neoplastic syndrome (ClinVar).

How common is PRKAR1A p.Ala41= (c.123T>G) in the general population?

PRKAR1A p.Ala41= (c.123T>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Carney complex inherited?

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

PRKAR1A p.Ala41=

c.123T>G · rs1307987878 · VCV1090906

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Carney complex, type 1

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 -20	GERP -4
Overall
CADD	0.336	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,034 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,214 alleles · very rare exomes 2/1,460,854 · genomes 0/152,360 · joint denominator

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.Ala41=
Coding: c.123T>G
MANE Select: NM_002734
dbSNP: rs1307987878
Type: single nucleotide variant
Location: chr17:68515522 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 41: 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

Also linked: hereditary neoplastic syndrome

For Carney complex (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PRKAR1A p.Ala41Asp Uncertain significance ★★ ⚠ same residue
PRKAR1A p.Ala41Thr Uncertain significance ★★ ⚠ same residue
PRKAR1A p.Ala41Val Uncertain significance ★ ⚠ same residue
WIPI1 p.Ser41Cys 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

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-ala41 (accessed [today's date]).

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