Is PRKAR2A p.Pro107Ser (c.319C>T) pathogenic?

PRKAR2A p.Pro107Ser (c.319C>T) is classified Uncertain significance in PRKAR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely pathogenic (0.9487); Very rare (popmax 0.00167%, amr).

How common is PRKAR2A p.Pro107Ser (c.319C>T) in the general population?

PRKAR2A p.Pro107Ser (c.319C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PRKAR2A p.Pro107Ser (c.319C>T)?

AlphaMissense predicts likely pathogenic (score 0.9487) — an in-silico prediction, not a clinical call.

PRKAR2A p.Pro107Ser

c.319C>T · rs746644588 · VCV2287936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9487	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -11.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 96 kb · p 0.003 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,926 alleles

Overall 6.23e-05% 1/1,605,416 alleles · very rare exomes 1/1,453,364 · genomes 0/152,052 · 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: PRKAR2A
Protein: p.Pro107Ser
Coding: c.319C>T
MANE Select: NM_004157
dbSNP: rs746644588
Type: single nucleotide variant
Location: chr3:48794029 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 8 PDB
Residue 107: the 'dimerization and phosphorylation' 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-pro107ser (accessed [today's date]).

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