Is PRKG1 p.Phe367= (c.1101C>T) pathogenic?

PRKG1 p.Phe367= (c.1101C>T) is classified Likely benign in PRKG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-30). Very rare (popmax 0.00659%, sas); Associated with aortic aneurysm, familial thoracic 8.

What condition is associated with PRKG1 p.Phe367= (c.1101C>T)?

PRKG1 p.Phe367= (c.1101C>T) is associated with aortic aneurysm, familial thoracic 8, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PRKG1 p.Phe367= (c.1101C>T) in the general population?

PRKG1 p.Phe367= (c.1101C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

PRKG1 p.Phe367=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1101C>T · rs752325371 · VCV1530435

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

aortic aneurysm, familial thoracic 8

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 2.3	GERP 2, phastCons 1
Overall
CADD	14.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,060 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000744% 12/1,613,452 alleles · very rare exomes 9/1,461,312 · genomes 3/152,140 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,177
African / African-American	0.00534%	18,720
East Asian	0.00223%	44,866
European (non-Finnish)	8.48e-05%	1,179,647

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: PRKG1
Protein: p.Phe367=
Coding: c.1101C>T
MANE Select: NM_006258
dbSNP: rs752325371
Type: single nucleotide variant
Location: chr10:52251594 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 26 PDB
Residue 367: the protein kinase domain; a binding site; a β-strand

Full PRKG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aortic aneurysm, familial thoracic 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

PRKG1 p.Phe367Leu Uncertain significance ★ ⚠ same residue
PRKG1 p.Arg192Gln Pathogenic ★★ same condition
PRKG1 c.1001+3A>G Uncertain significance ★★ same condition
PRKG1 c.1832+5G>A Uncertain significance ★★ same condition
PRKG1 c.478+4C>T Uncertain significance ★★ same condition
PRKG1 c.478+5G>A Uncertain significance ★★ same condition
PRKG1 c.840+5G>T Uncertain significance ★★ same condition
PRKG1 c.935+5G>A Uncertain significance ★★ 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/prkg1-p-phe367 (accessed [today's date]).

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