Is COL5A2 p.Ala352= (c.1056T>G) pathogenic?

COL5A2 p.Ala352= (c.1056T>G) is classified Conflicting classifications of pathogenicity in COL5A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-06-05). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL5A2 p.Ala352= (c.1056T>G)?

COL5A2 p.Ala352= (c.1056T>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL5A2 p.Ala352= (c.1056T>G) in the general population?

COL5A2 p.Ala352= (c.1056T>G) is absent from gnomAD v4.1 (gnomAD).

COL5A2 p.Ala352=

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.1056T>G · rs863223488 · VCV213093

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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 0.91	GERP -1.4, phastCons 0.99
Overall
CADD	10.48	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: COL5A2
Protein: p.Ala352=
Coding: c.1056T>G
MANE Select: NM_000393
dbSNP: rs863223488
Type: single nucleotide variant
Location: chr2:189078519 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 352: 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 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
COL5A2 p.Ala196Pro Uncertain significance ★★ ⚠ same condition
COL5A2 p.Ala592Thr 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-ala352 (accessed [today's date]).

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