Is PRKAR1A p.Pro84Ser (c.250C>T) pathogenic?

PRKAR1A p.Pro84Ser (c.250C>T) is classified Uncertain significance in PRKAR1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1378); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Pro84Ser (c.250C>T)?

PRKAR1A p.Pro84Ser (c.250C>T) is associated with hereditary neoplastic syndrome, Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Pro84Ser (c.250C>T) in the general population?

PRKAR1A p.Pro84Ser (c.250C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAR1A p.Pro84Ser (c.250C>T)?

AlphaMissense predicts likely benign (score 0.1378) — an in-silico prediction, not a clinical call.

PRKAR1A p.Pro84Ser

c.250C>T · rs1600478753 · VCV821396

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1378 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1378	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 7,453 bp · p 0.48 · regional, not allelic
Overall
CADD	21.7	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: PRKAR1A
Protein: p.Pro84Ser
Coding: c.250C>T
MANE Select: NM_002734
dbSNP: rs1600478753
Type: single nucleotide variant
Location: chr17:68522828 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 84: the 'dimerization and phosphorylation' region; the 'disordered' region

Full PRKAR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Carney complex, type 1

Similar variants

PRKAR1A p.Pro84= Likely benign ★★ same residue
PRKAR1A c.502+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A c.549+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A c.891+1G>A Likely pathogenic ★★ same condition
PRKAR1A c.891+3A>G Likely pathogenic ★★ same condition
PRKAR1A c.892-2A>G Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A p.Arg16Ter Pathogenic ★★ same condition
PRKAR1A p.Arg228Ter Pathogenic ★★ 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/prkar1a-p-pro84ser (accessed [today's date]).

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