Is COL3A1 p.Pro830Arg (c.2489C>G) pathogenic?

COL3A1 p.Pro830Arg (c.2489C>G) is classified Uncertain significance in COL3A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-20). AlphaMissense: likely benign (0.157); No allele count reported in gnomAD v4.1 (AN 1,551,680); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is COL3A1 p.Pro830Arg (c.2489C>G) in the general population?

COL3A1 p.Pro830Arg (c.2489C>G) is no allele count reported in gnomAD v4.1 (AN 1,551,680) (gnomAD).

What do computational predictors say about COL3A1 p.Pro830Arg (c.2489C>G)?

AlphaMissense predicts likely benign (score 0.157) — an in-silico prediction, not a clinical call.

COL3A1 p.Pro830Arg

Q: What condition is associated with COL3A1 p.Pro830Arg (c.2489C>G)?

COL3A1 p.Pro830Arg (c.2489C>G) 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.2489C>G · rs886038849 · VCV1792028

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.157 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,680)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.157	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 15 kb · p 5.1e-19 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,551,680). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL3A1
Protein: p.Pro830Arg
Coding: c.2489C>G
MANE Select: NM_000090
dbSNP: rs886038849
Type: single nucleotide variant
Location: chr2:189002998 (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.Pro830= Conflicting classifications of pathogenicity ★ 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-pro830arg (accessed [today's date]).

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