Is COL5A2 p.Pro467= (c.1401G>A) pathogenic?

COL5A2 p.Pro467= (c.1401G>A) is classified Conflicting classifications of pathogenicity in COL5A2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2023-05-13). Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome, classic type, 1.

What condition is associated with COL5A2 p.Pro467= (c.1401G>A)?

COL5A2 p.Pro467= (c.1401G>A) is associated with Ehlers-Danlos syndrome, classic type, 1, Ehlers-Danlos syndrome, classic type, 2 (ClinVar).

How common is COL5A2 p.Pro467= (c.1401G>A) in the general population?

COL5A2 p.Pro467= (c.1401G>A) is absent from gnomAD v4.1 (gnomAD).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL5A2 p.Pro467=

c.1401G>A · rs1553515794 · VCV546102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Ehlers-Danlos syndrome, classic type, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.42	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.69	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 2.5, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL5A2
Protein: p.Pro467=
Coding: c.1401G>A
MANE Select: NM_000393
dbSNP: rs1553515794
Type: single nucleotide variant
Location: chr2:189068015 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 467: the 'disordered' region

Full COL5A2 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: Ehlers-Danlos syndrome, classic type, 2

For Classical Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

COL5A2 p.Pro467Leu Benign/Likely benign ★★ same residue
COL5A2 p.Pro467Ser Uncertain significance ★ ⚠ same residue
COL5A2 c.1159-1G>A Likely pathogenic ★★ same condition
COL5A2 c.369+1G>T Likely pathogenic ★★ same condition
COL5A2 p.Gly252Cys Pathogenic/Likely pathogenic ★★ same condition
COL5A2 p.Pro659= Pathogenic ★★ same condition
COL5A2 c.1005+4T>C Uncertain significance ★★ same condition
COL5A2 c.1618-7G>A 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/col5a2-p-pro467 (accessed [today's date]).

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