Is PRKG1 p.Asp33= (c.99T>C) pathogenic?

PRKG1 p.Asp33= (c.99T>C) is classified Likely benign in PRKG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-15). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is PRKG1 p.Asp33= (c.99T>C) in the general population?

PRKG1 p.Asp33= (c.99T>C) is absent from gnomAD v4.1 (gnomAD).

PRKG1 p.Asp33=

Q: What condition is associated with PRKG1 p.Asp33= (c.99T>C)?

PRKG1 p.Asp33= (c.99T>C) is associated with familial thoracic aortic aneurysm and aortic dissection, aortic aneurysm, familial thoracic 8 (ClinVar).

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.99T>C · rs1589133712 · VCV742630

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 0.46	GERP -1.2, phastCons 1
Overall
CADD	12.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKG1
Protein: p.Asp33=
Coding: c.99T>C
MANE Select: NM_006258
dbSNP: rs1589133712
Type: single nucleotide variant
Location: chr10:51074689 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 26 PDB
Residue 33: the 'required for dimerization' region; an α-helix; the 'leucine-zipper' region

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

Disease context

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

Also linked: aortic aneurysm, familial thoracic 8

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

PRKG1 p.Asp33His 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-asp33 (accessed [today's date]).

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