Is COL5A1 p.Val596= (c.1788G>T) pathogenic?

COL5A1 p.Val596= (c.1788G>T) is classified Likely benign in COL5A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.000932%, nfe); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL5A1 p.Val596= (c.1788G>T)?

COL5A1 p.Val596= (c.1788G>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL5A1 p.Val596= (c.1788G>T) in the general population?

COL5A1 p.Val596= (c.1788G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

COL5A1 p.Val596=

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.1788G>T · rs368129835 · VCV2448290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000932%, 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 -0.029	GERP -3.4, phastCons 0.34
Overall
CADD	3.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,048 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,858 alleles · very rare exomes 10/1,461,620 · genomes 1/152,238 · 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: COL5A1
Protein: p.Val596=
Coding: c.1788G>T
MANE Select: NM_000093
dbSNP: rs368129835
Type: single nucleotide variant
Location: chr9:134754287 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 596: the 'disordered' region; the 'triple-helical region' 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.Val596Ala Conflicting classifications of pathogenicity ★ ⚠ 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
COL5A1 c.1828-3C>G 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/col5a1-p-val596 (accessed [today's date]).

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