Is COL3A1 c.1663-9del pathogenic?

COL3A1 c.1663-9del is classified Likely benign in COL3A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-13). Very rare (popmax 0.0011%, sas); Associated with Ehlers-Danlos syndrome, vascular type.

What condition is associated with COL3A1 c.1663-9del?

COL3A1 c.1663-9del is associated with Ehlers-Danlos syndrome, vascular type, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL3A1 c.1663-9del in the general population?

COL3A1 c.1663-9del is very rare (popmax 0.0011%, sas) (gnomAD).

How is Vascular Ehlers-Danlos syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL3A1 c.1663-9del

rs770372880 · VCV924665

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Ehlers-Danlos syndrome, vascular type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	acceptor -9	acceptor splice region (-9, within the last 20 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.054	GERP -3.8

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,784 alleles

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

Overall 0.000187% 3/1,604,170 alleles · very rare exomes 3/1,453,556 · genomes 0/150,614 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,784
European (non-Finnish)	0.000171%	586,287

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: COL3A1
Coding: c.1663-9del
MANE Select: NM_000090
dbSNP: rs770372880
Type: Deletion
Location: chr2:188996384 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB

Full COL3A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, vascular type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Vascular Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

COL3A1 c.3257_3266delGTCCTCAAGG Pathogenic/Likely pathogenic ★★ same condition
COL3A1 p.Glu1246fs Pathogenic/Likely pathogenic ★★ same condition
COL3A1 p.Gly1146fs Pathogenic ★★ same condition
COL3A1 p.Gly186fs Pathogenic ★★ same condition
COL3A1 p.Gly564fs Pathogenic ★★ same condition
COL3A1 p.Gly636fs Pathogenic/Likely pathogenic ★★ same condition
COL3A1 p.Pro551fs Pathogenic ★★ same condition
COL3A1 p.Pro565fs Pathogenic/Likely 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/col3a1-c-1663-minus-9del (accessed [today's date]).

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