Is COL5A1 p.Pro770= (c.2310T>A) pathogenic?

COL5A1 p.Pro770= (c.2310T>A) is classified Benign/Likely benign in COL5A1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0992%, mid); Associated with Ehlers-Danlos syndrome, classic type, 1.

What condition is associated with COL5A1 p.Pro770= (c.2310T>A)?

COL5A1 p.Pro770= (c.2310T>A) is associated with Ehlers-Danlos syndrome, classic type, 1, familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome (ClinVar).

How common is COL5A1 p.Pro770= (c.2310T>A) in the general population?

COL5A1 p.Pro770= (c.2310T>A) is ultra-rare (popmax 0.0992%, mid) (gnomAD).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL5A1 p.Pro770=

c.2310T>A · rs377123592 · VCV212893

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0992%, mid)

Conditions

Ehlers-Danlos syndrome, classic type, 1

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 -1.4	GERP -3.4, phastCons 0.001
Overall
CADD	7.447	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0992% Middle Eastern · 6/6,048 alleles

Filtering AF 0.0432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.00595% 96/1,613,876 alleles · ultra-rare exomes 89/1,461,680 · genomes 7/152,196 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0992%	1,008
Finnishnot grpmax-eligible	0.0125%	7,987
South Asian	0.011%	9,109
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0064%	15,618
European (non-Finnish)	0.00525%	19,033

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.Pro770=
Coding: c.2310T>A
MANE Select: NM_000093
dbSNP: rs377123592
Type: single nucleotide variant
Location: chr9:134772813 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 770: the 'disordered' region; the 'triple-helical region' region

Full COL5A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, classic type, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection Ehlers-Danlos syndrome fibromuscular dysplasia, multifocal

For Classical Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

COL5A1 p.Pro770Thr Uncertain significance ★ ⚠ same residue
COL5A1 p.Pro770Arg Uncertain significance ★ ⚠ same residue
COL5A1 c.1332+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.1720-11T>A Likely pathogenic ★★ same condition
COL5A1 c.2034+1G>A Pathogenic ★★ same condition
COL5A1 c.2430+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.2430+1G>C Pathogenic ★★ same condition
COL5A1 c.2701-25T>G 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/col5a1-p-pro770 (accessed [today's date]).

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