Is COL3A1 p.Pro197= (c.591A>G) pathogenic?

COL3A1 p.Pro197= (c.591A>G) is classified Likely benign in COL3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-09). Very rare (popmax 0.000256%, nfe); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL3A1 p.Pro197= (c.591A>G)?

COL3A1 p.Pro197= (c.591A>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL3A1 p.Pro197= (c.591A>G) in the general population?

COL3A1 p.Pro197= (c.591A>G) is very rare (popmax 0.000256%, nfe) (gnomAD).

COL3A1 p.Pro197=

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.591A>G · rs1261508252 · VCV922149

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

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 -0.24	GERP -1.9, phastCons 0.003
Overall
CADD	8.583	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000256% European (non-Finnish) · 3/1,172,058 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,604,430 alleles · very rare exomes 3/1,452,158 · genomes 0/152,272 · 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: COL3A1
Protein: p.Pro197=
Coding: c.591A>G
MANE Select: NM_000090
dbSNP: rs1261508252
Type: single nucleotide variant
Location: chr2:188988598 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB
Residue 197: a modified residue (4-hydroxyproline); the 'disordered' region; the 'triple-helical region' region

Full COL3A1 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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL3A1 p.Pro197Gln Uncertain significance ★ ⚠ same residue
COL3A1 c.1294-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1347+1G>A Pathogenic ★★ same condition
COL3A1 c.1348-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1662+1G>A Pathogenic ★★ same condition
COL3A1 c.2229+1G>A Likely pathogenic ★★ same condition
COL3A1 c.3093+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.3202-2A>G Pathogenic ★★ 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/col3a1-p-pro197 (accessed [today's date]).

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