Is COL3A1 p.Pro701= (c.2103T>C) pathogenic?

COL3A1 p.Pro701= (c.2103T>C) is classified Likely benign in COL3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-12). Ultra-rare (popmax 0.0165%, mid); Associated with Ehlers-Danlos syndrome, vascular type.

What condition is associated with COL3A1 p.Pro701= (c.2103T>C)?

COL3A1 p.Pro701= (c.2103T>C) is associated with Ehlers-Danlos syndrome, vascular type (ClinVar).

How common is COL3A1 p.Pro701= (c.2103T>C) in the general population?

COL3A1 p.Pro701= (c.2103T>C) is ultra-rare (popmax 0.0165%, mid) (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 p.Pro701=

c.2103T>C · rs1688401379 · VCV1548823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Ehlers-Danlos syndrome, vascular type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -1.2, phastCons 0.001
Overall
CADD	6.894	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Overall 0.000187% 3/1,606,172 alleles · ultra-rare exomes 3/1,453,902 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.00161%	62,188
European (non-Finnish)	8.5e-05%	1,176,148

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
Protein: p.Pro701=
Coding: c.2103T>C
MANE Select: NM_000090
dbSNP: rs1688401379
Type: single nucleotide variant
Location: chr2:188999365 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB
Residue 701: a modified residue (4-hydroxyproline); a UniProt-annotated variant site (in pmgedsv); the 'disordered' region; the 'triple-helical region' region

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

For Vascular Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

COL3A1 p.Pro701Ala Uncertain significance ★★ ⚠ same residue
COL3A1 p.Pro701fs Pathogenic ★★ same residue
COL3A1 c.1051-1G>C Likely pathogenic ★★ same condition
COL3A1 c.1294-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1347+1G>A Pathogenic ★★ same condition
COL3A1 c.1348-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1662+1G>A Pathogenic ★★ same condition
COL3A1 c.1663-1G>A 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-p-pro701 (accessed [today's date]).

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