Is PRKG1 p.Pro72= (c.216G>A) pathogenic?

PRKG1 p.Pro72= (c.216G>A) is classified Likely benign in PRKG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-04). Very rare (popmax 0.00167%, amr); Associated with aortic aneurysm, familial thoracic 8.

What condition is associated with PRKG1 p.Pro72= (c.216G>A)?

PRKG1 p.Pro72= (c.216G>A) is associated with aortic aneurysm, familial thoracic 8 (ClinVar).

How common is PRKG1 p.Pro72= (c.216G>A) in the general population?

PRKG1 p.Pro72= (c.216G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

PRKG1 p.Pro72=

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.216G>A · rs2132804663 · VCV1631612

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 3.5	GERP 0.4, phastCons 1
Overall
CADD	13.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,982 alleles

Overall 6.2e-05% 1/1,613,776 alleles · very rare exomes 1/1,461,506 · 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: PRKG1
Protein: p.Pro72=
Coding: c.216G>A
MANE Select: NM_006258
dbSNP: rs2132804663
Type: single nucleotide variant
Location: chr10:51074806 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 26 PDB
Residue 72: the 'required for dimerization' region; the 'autoinhibitory domain' region

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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

PRKG1 p.Pro72Ala Uncertain significance ★ same residue
PRKG1 p.Pro72Thr Uncertain significance ★ same residue
PRKG1 p.Pro72Arg Uncertain significance ★ same residue
PRKG1 p.Pro72Gln 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

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-pro72 (accessed [today's date]).

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