Is PRKAR2A p.Asp69Ala (c.206A>C) pathogenic?

PRKAR2A p.Asp69Ala (c.206A>C) is classified Uncertain significance in PRKAR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). AlphaMissense: likely benign (0.0712); Absent from gnomAD v4.1.

How common is PRKAR2A p.Asp69Ala (c.206A>C) in the general population?

PRKAR2A p.Asp69Ala (c.206A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAR2A p.Asp69Ala (c.206A>C)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

PRKAR2A p.Asp69Ala

c.206A>C · rs2470990671 · VCV2494283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -4.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -3.6
Regional constraint	o/e 0.87	unconstrained · MANE · 96 kb · p 0.003 · regional, not allelic
Overall
CADD	9.703	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKAR2A
Protein: p.Asp69Ala
Coding: c.206A>C
MANE Select: NM_004157
dbSNP: rs2470990671
Type: single nucleotide variant
Location: chr3:48847391 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 8 PDB
Residue 69: the 'dimerization and phosphorylation' region; the 'disordered' region

Full PRKAR2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAR2A p.Ala45Val Uncertain significance ★ ⚠ same type
PRKAR2A p.Ala47Val Uncertain significance ★ ⚠ same type
PRKAR2A p.Ala52Val Uncertain significance ★ ⚠ same type
PRKAR2A p.Ala74Ser Uncertain significance ★ ⚠ same type
PRKAR2A p.Arg158Lys Uncertain significance ★ ⚠ same type
PRKAR2A p.Arg195Cys Uncertain significance ★ ⚠ same type
PRKAR2A p.Arg195Gly Uncertain significance ★ same type
PRKAR2A p.Arg203Cys 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/prkar2a-p-asp69ala (accessed [today's date]).

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