Is PRKG1 p.Pro103Ser (c.307C>T) pathogenic?

PRKG1 p.Pro103Ser (c.307C>T) is classified Uncertain significance in PRKG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-22). Very rare (popmax 0.00102%, nfe); Associated with aortic aneurysm, familial thoracic 8.

What condition is associated with PRKG1 p.Pro103Ser (c.307C>T)?

PRKG1 p.Pro103Ser (c.307C>T) is associated with aortic aneurysm, familial thoracic 8, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PRKG1 p.Pro103Ser (c.307C>T) in the general population?

PRKG1 p.Pro103Ser (c.307C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

PRKG1 p.Pro103Ser

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.307C>T · rs201361942 · VCV2098464

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

aortic aneurysm, familial thoracic 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.299	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,206 kb · p 7e-12 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,173,122 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000431%

Overall 0.000748% 12/1,604,040 alleles · very rare

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_006258
dbSNP: rs201361942
Type: single nucleotide variant
Location: chr10:51074897 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 26 PDB
Residue 103: a turn; 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.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
PRKG1 p.Ala356Val 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-pro103ser (accessed [today's date]).

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