Is PRKAR1A p.Arg306Gln (c.917G>A) pathogenic?

PRKAR1A p.Arg306Gln (c.917G>A) is classified Uncertain significance in PRKAR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). AlphaMissense: likely benign (0.2168); Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Arg306Gln (c.917G>A)?

PRKAR1A p.Arg306Gln (c.917G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PRKAR1A p.Arg306Gln (c.917G>A) in the general population?

PRKAR1A p.Arg306Gln (c.917G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PRKAR1A p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.2168) — an in-silico prediction, not a clinical call.

PRKAR1A p.Arg306Gln

c.917G>A · rs1568702564 · VCV633375

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2168	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 7,428 bp · p 4.1e-27 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,912 alleles

Overall 6.2e-05% 1/1,613,936 alleles · very rare exomes 1/1,461,772 · genomes 0/152,164 · 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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_002734
dbSNP: rs1568702564
Type: single nucleotide variant
Location: chr17:68529945 (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

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

Similar variants

PRKAR1A p.Arg306Trp Uncertain significance ★ same residue
PRKAR1A p.Arg306= Likely benign ★ same residue
PRKAR1A p.Arg306Gly Uncertain significance ★ same residue
PRKAR1A c.502+1G>A Pathogenic/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.Arg97Ter 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-arg306gln (accessed [today's date]).

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