Is PRKAR1A p.Ser378= (c.1134A>G) pathogenic?

PRKAR1A p.Ser378= (c.1134A>G) is classified Likely benign in PRKAR1A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.01%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Ser378= (c.1134A>G)?

PRKAR1A p.Ser378= (c.1134A>G) is associated with hereditary neoplastic syndrome, Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Ser378= (c.1134A>G) in the general population?

PRKAR1A p.Ser378= (c.1134A>G) is very rare (popmax 0.01%, amr) (gnomAD).

PRKAR1A p.Ser378=

c.1134A>G · rs1001156045 · VCV496167

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -4
Overall
CADD	2.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,010 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,614,068 alleles · very rare exomes 6/1,461,798 · genomes 0/152,270 · 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: PRKAR1A
Protein: p.Ser378=
Coding: c.1134A>G
MANE Select: NM_002734
dbSNP: rs1001156045
Type: single nucleotide variant
Location: chr17:68530437 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB

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.Ser378Leu Uncertain significance ★★ same residue
PRKAR1A p.Ser378Ter Uncertain significance ★ 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

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-ser378 (accessed [today's date]).

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