Is PRKAR1A p.Phe54= (c.162T>C) pathogenic?

PRKAR1A p.Phe54= (c.162T>C) is classified Likely benign in PRKAR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-30). Very rare (popmax 0.00134%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Phe54= (c.162T>C)?

PRKAR1A p.Phe54= (c.162T>C) is associated with hereditary neoplastic syndrome, Carney complex, type 1 (ClinVar).

How common is PRKAR1A p.Phe54= (c.162T>C) in the general population?

PRKAR1A p.Phe54= (c.162T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

PRKAR1A p.Phe54=

c.162T>C · rs1220727515 · VCV2048583

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.4	GERP -4.3
Overall
CADD	0.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,876 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,612,384 alleles · very rare exomes 7/1,460,182 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,876
European (non-Finnish)	0.000593%	168,565

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.Phe54=
Coding: c.162T>C
MANE Select: NM_002734
dbSNP: rs1220727515
Type: single nucleotide variant
Location: chr17:68515561 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 54: the 'dimerization and phosphorylation' 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.Phe54Leu 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
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-phe54 (accessed [today's date]).

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