Is PRKG1 p.Pro136= (c.408G>A) pathogenic?

PRKG1 p.Pro136= (c.408G>A) is classified Benign in PRKG1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.51%, mid); Associated with aortic aneurysm, familial thoracic 8.

What condition is associated with PRKG1 p.Pro136= (c.408G>A)?

PRKG1 p.Pro136= (c.408G>A) is associated with aortic aneurysm, familial thoracic 8, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PRKG1 p.Pro136= (c.408G>A) in the general population?

PRKG1 p.Pro136= (c.408G>A) is low-frequency (popmax 2.51%, mid) (gnomAD).

PRKG1 p.Pro136=

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.408G>A · rs55806342 · VCV220801

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.51%, mid)

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 -6.1	GERP -3.5
Overall
CADD	1.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.51% Middle Eastern · 152/6,050 alleles

Filtering AF 2.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.17%

Overall 1.99% 32,107/1,612,374 alleles · low-frequency exomes 29,480/1,460,330 · genomes 2,627/152,044 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.09%	32
Ashkenazi Jewishnot grpmax-eligible	2.78%	36
Middle Easterngrpmax	2.51%	40
European (non-Finnish)	2.2%	45
Remaining individualsnot grpmax-eligible	2.07%	48
Admixed American	1.26%	79
Amishnot grpmax-eligible	1.21%	83
South Asian	0.858%	117
African / African-American	0.494%	202
East Asian	0.00223%	44,864

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro136=
Coding: c.408G>A
MANE Select: NM_006258
dbSNP: rs55806342
Type: single nucleotide variant
Location: chr10:51153260 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 26 PDB
Residue 136: a β-strand; the 'cgmp-binding, high affinity' 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

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.Pro136Leu Uncertain significance ★★ ⚠ same residue
PRKG1 p.Pro136Ser 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

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-pro136 (accessed [today's date]).

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