Is COL5A2 p.Pro514= (c.1542T>C) pathogenic?

COL5A2 p.Pro514= (c.1542T>C) is classified Benign/Likely benign in COL5A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-26). Ultra-rare (popmax 0.0535%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is COL5A2 p.Pro514= (c.1542T>C) in the general population?

COL5A2 p.Pro514= (c.1542T>C) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

COL5A2 p.Pro514=

Q: What condition is associated with COL5A2 p.Pro514= (c.1542T>C)?

COL5A2 p.Pro514= (c.1542T>C) 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.1542T>C · rs770622592 · VCV459728

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.3	GERP 1.3, phastCons 1
Overall
CADD	13.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,878 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00161% 26/1,614,016 alleles · ultra-rare exomes 24/1,461,824 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,870
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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: COL5A2
Protein: p.Pro514=
Coding: c.1542T>C
MANE Select: NM_000393
dbSNP: rs770622592
Type: single nucleotide variant
Location: chr2:189066411 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 514: the 'disordered' region

Full COL5A2 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

COL5A2 p.Pro514Leu Uncertain significance ★ ⚠ same residue
COL5A2 c.1159-1G>A Likely pathogenic ★★ same condition
COL5A2 c.369+1G>T Likely pathogenic ★★ same condition
COL5A2 p.Gly252Cys Pathogenic/Likely pathogenic ★★ same condition
COL5A2 p.Pro659= Pathogenic ★★ same condition
COL5A2 c.1005+4T>C Uncertain significance ★★ same condition
COL5A2 c.1618-7G>A Uncertain significance ★★ same condition
COL5A2 c.1716+5G>A Uncertain significance ★★ 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/col5a2-p-pro514 (accessed [today's date]).

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