Is COL5A1 p.Pro693= (c.2079C>T) pathogenic?

COL5A1 p.Pro693= (c.2079C>T) is classified Likely benign in COL5A1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00989%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is COL5A1 p.Pro693= (c.2079C>T) in the general population?

COL5A1 p.Pro693= (c.2079C>T) is very rare (popmax 0.00989%, sas) (gnomAD).

COL5A1 p.Pro693=

Q: What condition is associated with COL5A1 p.Pro693= (c.2079C>T)?

COL5A1 p.Pro693= (c.2079C>T) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, classic type, 1 (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.2079C>T · rs186098435 · VCV386635

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

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 -12	GERP -2.7
Overall
CADD	0.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00989% South Asian · 9/90,968 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00192% 31/1,612,842 alleles · very rare exomes 24/1,460,496 · genomes 7/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,108
East Asian	0.00669%	14,953
Admixed American	0.00667%	14,983
African / African-American	0.00133%	75,038
European (non-Finnish)	0.00119%	84,224

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: COL5A1
Protein: p.Pro693=
Coding: c.2079C>T
MANE Select: NM_000093
dbSNP: rs186098435
Type: single nucleotide variant
Location: chr9:134765725 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 693: the 'disordered' region; the 'triple-helical region' region

Full COL5A1 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: Ehlers-Danlos syndrome, classic type, 1

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL5A1 c.1332+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.1720-11T>A Likely pathogenic ★★ same condition
COL5A1 c.2034+1G>A Pathogenic ★★ same condition
COL5A1 c.2430+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.2430+1G>C Pathogenic ★★ same condition
COL5A1 c.2701-25T>G Pathogenic ★★ same condition
COL5A1 c.4338+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.5067+1G>A Likely 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/col5a1-p-pro693 (accessed [today's date]).

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