Is COL5A1 p.Pro500= (c.1500C>G) pathogenic?

COL5A1 p.Pro500= (c.1500C>G) is classified Likely benign in COL5A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL5A1 p.Pro500= (c.1500C>G)?

COL5A1 p.Pro500= (c.1500C>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL5A1 p.Pro500= (c.1500C>G) in the general population?

COL5A1 p.Pro500= (c.1500C>G) is absent from gnomAD v4.1 (gnomAD).

COL5A1 p.Pro500=

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.1500C>G · VCV4635348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 -0.48	GERP -3.2, phastCons 0.06
Overall
CADD	6.157	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: COL5A1
Protein: p.Pro500=
Coding: c.1500C>G
MANE Select: NM_000093
Type: single nucleotide variant
Location: chr9:134750547 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 500: the 'interrupted collagenous region' region; the 'disordered' 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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL5A1 p.Pro500Ser Uncertain significance ★★ ⚠ same residue
COL5A1 p.Pro500Leu Benign ★ ⚠ same residue
COL5A1 c.1720-11T>A Likely pathogenic ★★ same condition
COL5A1 c.655-1G>C Likely pathogenic ★★ same condition
COL5A1 c.655-2A>T Likely pathogenic ★★ same condition
COL5A1 p.Arg1062Ter Pathogenic ★★ same condition
COL5A1 p.Arg594Ter Pathogenic/Likely pathogenic ★★ same condition
COL5A1 p.Arg912Ter 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-pro500 (accessed [today's date]).

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