Is COL5A2 p.Pro164= (c.492A>T) pathogenic?

COL5A2 p.Pro164= (c.492A>T) is classified Likely benign in COL5A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00017%, nfe); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL5A2 p.Pro164= (c.492A>T)?

COL5A2 p.Pro164= (c.492A>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL5A2 p.Pro164= (c.492A>T) in the general population?

COL5A2 p.Pro164= (c.492A>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

COL5A2 p.Pro164=

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.492A>T · VCV3495578

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, 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 -2.3	GERP -4.7
Overall
CADD	6.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,410 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,606,790 alleles · very rare exomes 2/1,454,478 · genomes 0/152,312 · joint denominator

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.Pro164=
Coding: c.492A>T
MANE Select: NM_000393
Type: single nucleotide variant
Location: chr2:189092385 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 164: 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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL5A2 p.Pro164Ala Uncertain significance ★★ ⚠ same residue
COL5A2 p.Pro164Gln Uncertain significance ★★ ⚠ same residue
COL5A2 c.1005+4T>C Uncertain significance ★★ same condition
COL5A2 c.1618-7G>A Uncertain significance ★★ same condition
COL5A2 c.2031+3A>G Uncertain significance ★★ same condition
COL5A2 c.798+5G>A Uncertain significance ★★ same condition
COL5A2 p.Ala1076Val Uncertain significance ★★ ⚠ same condition
COL5A2 p.Ala1323Thr 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-pro164 (accessed [today's date]).

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