Is PRKAR1B p.Pro308Arg (c.923C>G) pathogenic?

PRKAR1B p.Pro308Arg (c.923C>G) is classified Uncertain significance in PRKAR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-04). AlphaMissense: likely benign (0.1372); Very rare (popmax 0.000174%, nfe).

How common is PRKAR1B p.Pro308Arg (c.923C>G) in the general population?

PRKAR1B p.Pro308Arg (c.923C>G) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about PRKAR1B p.Pro308Arg (c.923C>G)?

AlphaMissense predicts likely benign (score 0.1372) — an in-silico prediction, not a clinical call.

PRKAR1B p.Pro308Arg

c.923C>G · VCV4862522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1372	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -11.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.35 · regional, not allelic
Overall
CADD	16.94	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

Grpmax group 0.000174% European (non-Finnish) · 2/1,151,618 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000128% 2/1,559,782 alleles · very rare exomes 2/1,407,548 · genomes 0/152,234 · 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: PRKAR1B
Protein: p.Pro308Arg
Coding: c.923C>G
MANE Select: NM_001164760
Type: single nucleotide variant
Location: chr7:551439 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 3 PDB

Full PRKAR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAR1B p.Pro308= Likely benign ★ same residue
PRKAR1B p.Arg335Trp Pathogenic/Likely pathogenic ★★ same type
DNAAF5 p.Asp87Tyr Uncertain significance ★★ ⚠ same type
DNAAF5 p.Cys138Gly Uncertain significance ★★ ⚠ same type
DNAAF5 p.Glu8Ala Uncertain significance ★★ ⚠ same type
DNAAF5 p.Gly150Arg Uncertain significance ★★ ⚠ same type
DNAAF5 p.Val6Ala Uncertain significance ★★ ⚠ same type
PRKAR1B p.Ala204Val Uncertain significance ★★ ⚠ same type

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/prkar1b-p-pro308arg (accessed [today's date]).

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