Is COL3A1 p.Pro830= (c.2490G>A) pathogenic?

COL3A1 p.Pro830= (c.2490G>A) is classified Conflicting classifications of pathogenicity in COL3A1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00654%, nfe); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is COL3A1 p.Pro830= (c.2490G>A) in the general population?

COL3A1 p.Pro830= (c.2490G>A) is very rare (popmax 0.00654%, nfe) (gnomAD).

COL3A1 p.Pro830=

Q: What condition is associated with COL3A1 p.Pro830= (c.2490G>A)?

COL3A1 p.Pro830= (c.2490G>A) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, vascular type (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.2490G>A · rs777361888 · VCV234653

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00654%, 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 -5.6	GERP -3.8
Overall
CADD	7.405	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00654% European (non-Finnish) · 75/1,147,058 alleles

Filtering AF 0.00534% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00487%

Overall 0.00535% 83/1,551,640 alleles · very rare exomes 80/1,399,514 · genomes 3/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00654%	15,294
Remaining individualsnot grpmax-eligible	0.00499%	20,034
South Asian	0.00476%	21,017
African / African-American	0.00137%	73,034

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.Pro830=
Coding: c.2490G>A
MANE Select: NM_000090
dbSNP: rs777361888
Type: single nucleotide variant
Location: chr2:189002999 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB
Residue 830: a modified residue (4-hydroxyproline); a UniProt-annotated variant site (in pmgedsv); a UniProt-annotated variant site (in edsvasc); 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

Also linked: Ehlers-Danlos syndrome, vascular type

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL3A1 p.Pro830Arg Uncertain significance ★★ ⚠ same residue
COL3A1 p.Pro830Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
COL3A1 c.1051-1G>C Likely pathogenic ★★ same condition
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.1663-1G>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/col3a1-p-pro830 (accessed [today's date]).

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