Is COL5A1 p.Pro147= (c.441T>C) pathogenic?

COL5A1 p.Pro147= (c.441T>C) is classified Conflicting classifications of pathogenicity in COL5A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-27). Very rare (popmax 0.000763%, nfe); Associated with Ehlers-Danlos syndrome, classic type, 1.

What condition is associated with COL5A1 p.Pro147= (c.441T>C)?

COL5A1 p.Pro147= (c.441T>C) 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.Pro147= (c.441T>C) in the general population?

COL5A1 p.Pro147= (c.441T>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL5A1 p.Pro147=

c.441T>C · rs1833615155 · VCV1702214

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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 -7.6	GERP -4.1
Overall
CADD	0.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,020 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000754% 11/1,459,842 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)grpmax	0.000763%	131,113

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro147=
Coding: c.441T>C
MANE Select: NM_000093
dbSNP: rs1833615155
Type: single nucleotide variant
Location: chr9:134700072 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB
Residue 147: the laminin g-like domain

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

For Classical Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

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
COL5A1 c.4338+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL5A1 c.5067+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/col5a1-p-pro147 (accessed [today's date]).

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