Is PRKAR1B p.Arg306Gln (c.917G>A) pathogenic?

PRKAR1B p.Arg306Gln (c.917G>A) is classified Pathogenic in PRKAR1B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-31). AlphaMissense: likely benign (0.2498); Very rare (popmax 0.00194%, amr); Associated with Marbach-Schaaf neurodevelopmental syndrome.

What condition is associated with PRKAR1B p.Arg306Gln (c.917G>A)?

PRKAR1B p.Arg306Gln (c.917G>A) is associated with Marbach-Schaaf neurodevelopmental syndrome (ClinVar).

How common is PRKAR1B p.Arg306Gln (c.917G>A) in the general population?

PRKAR1B p.Arg306Gln (c.917G>A) is very rare (popmax 0.00194%, amr) (gnomAD).

How is Marbach-Schaaf neurodevelopmental syndrome inherited?

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

What do computational predictors say about PRKAR1B p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.2498) — an in-silico prediction, not a clinical call.

PRKAR1B p.Arg306Gln

c.917G>A · rs866622752 · VCV2444586

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00194%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Marbach-Schaaf neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.2498	likely benign ⚠ discordant with ClinVar
REVEL	0.44	indeterminate
SaProt	LLR -7.08	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 7.4	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.35 · regional, not allelic
Overall
CADD	25.2	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 0.00194% Admixed American · 1/51,470 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000385% 6/1,558,612 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00194%	51,470
Remaining individualsnot grpmax-eligible	0.00166%	60,376
European (non-Finnish)	0.000348%	287,766

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_001164760
dbSNP: rs866622752
Type: single nucleotide variant
Location: chr7:551445 (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

Disease context

Marbach-Schaaf neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Marbach-Schaaf neurodevelopmental syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PRKAR1B p.Arg335Trp Pathogenic/Likely pathogenic ★★ same condition
PRKAR1B p.Arg305Cys Uncertain significance ★★ ⚠ same condition
PRKAR1B p.Trp190Ter Likely pathogenic ★ same condition
PRKAR1B p.Ala270Val Uncertain significance ★ ⚠ same condition
PRKAR1B p.Ala336Val Uncertain significance ★ ⚠ same condition
PRKAR1B p.Arg357Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKAR1B p.Glu196Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKAR1B p.Glu202Asp Uncertain significance ★ ⚠ 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/prkar1b-p-arg306gln (accessed [today's date]).

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