Is COL1A2 p.Pro482His (c.1445_1446delinsAC) pathogenic?

COL1A2 p.Pro482His (c.14451446delinsAC) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). Associated with Ehlers-Danlos syndrome, classic type, 1.

What condition is associated with COL1A2 p.Pro482His (c.1445_1446delinsAC)?

COL1A2 p.Pro482His (c.1445_1446delinsAC) is associated with Ehlers-Danlos syndrome, classic type, 1, osteogenesis imperfecta type 1 (ClinVar).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL1A2 p.Pro482His

c.1445_1446delinsAC · VCV3751670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic

Variant & gene context

Gene: COL1A2
Protein: p.Pro482His
Coding: c.1445_1446delinsAC
MANE Select: NM_000089
Type: Indel
Location: chr7:94412624 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 482: the 'disordered' region

Full COL1A2 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: osteogenesis imperfecta type 1

For Classical Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

COL1A2 p.Pro482= Benign ★★ same residue
COL1A2 p.Pro482Ser Uncertain significance ★ ⚠ same residue
COL1A2 p.Pro482Thr Uncertain significance ★ ⚠ same residue
COL1A2 c.1665+14_1665+15delinsCG Uncertain significance ★ same condition
COL1A2 p.Ala483Thr Uncertain significance ★ same condition
COL1A2 p.Cys1317Phe Uncertain significance ★ same condition
COL1A2 p.Val717_Pro719delinsArgGly Uncertain significance ★ same condition
COL1A2 p.Pro549Ala Likely benign ★ 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/col1a2-p-pro482his (accessed [today's date]).

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