Is PRKAR2A p.Ala52Val (c.155C>T) pathogenic?

PRKAR2A p.Ala52Val (c.155C>T) is classified Uncertain significance in PRKAR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.0833); Very rare (popmax 0.000516%, nfe).

How common is PRKAR2A p.Ala52Val (c.155C>T) in the general population?

PRKAR2A p.Ala52Val (c.155C>T) is very rare (popmax 0.000516%, nfe) (gnomAD).

What do computational predictors say about PRKAR2A p.Ala52Val (c.155C>T)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

PRKAR2A p.Ala52Val

c.155C>T · VCV3425097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000516%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -7.19	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 -0.59	GERP 2.4, phastCons 0.41
Regional constraint	o/e 0.87	unconstrained · MANE · 96 kb · p 0.003 · regional, not allelic
Overall
CADD	17.76	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 0.000516% European (non-Finnish) · 6/1,163,100 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.00042% 6/1,427,882 alleles · very rare

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: PRKAR2A
Protein: p.Ala52Val
Coding: c.155C>T
MANE Select: NM_004157
Type: single nucleotide variant
Location: chr3:48847442 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 8 PDB
Residue 52: 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.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
PRKAR2A p.Arg313Gly 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-ala52val (accessed [today's date]).

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