Is PRKAR1A p.Arg94= (c.282G>A) pathogenic?

PRKAR1A p.Arg94= (c.282G>A) is classified Likely benign in PRKAR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-29). Very rare (popmax 0.00769%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Arg94= (c.282G>A)?

PRKAR1A p.Arg94= (c.282G>A) is associated with hereditary neoplastic syndrome, Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Arg94= (c.282G>A) in the general population?

PRKAR1A p.Arg94= (c.282G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

PRKAR1A p.Arg94=

c.282G>A · rs752243808 · VCV1574912

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.58	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.36	GERP -4.3, phastCons 0.012
Overall
CADD	6.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,080 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000496% 8/1,613,832 alleles · very rare exomes 6/1,461,626 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,011
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Arg94=
Coding: c.282G>A
MANE Select: NM_002734
dbSNP: rs752243808
Type: single nucleotide variant
Location: chr17:68522860 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 94: the 'dimerization and phosphorylation' region; the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Carney complex, type 1

Similar variants

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 c.892-2A>G Pathogenic/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-arg94 (accessed [today's date]).

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