Is COL1A2 p.Pro477fs (c.1430del) pathogenic?

COL1A2 p.Pro477fs (c.1430del) is classified Pathogenic in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). No gnomAD frequency available for this variant; Associated with Ehlers-Danlos syndrome, classic type, 1.

What condition is associated with COL1A2 p.Pro477fs (c.1430del)?

COL1A2 p.Pro477fs (c.1430del) is associated with Ehlers-Danlos syndrome, classic type, 1, osteogenesis imperfecta type 1 (ClinVar).

How common is COL1A2 p.Pro477fs (c.1430del) in the general population?

COL1A2 p.Pro477fs (c.1430del) is no gnomAD frequency available for this variant (gnomAD).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL1A2 p.Pro477fs

c.1430del · rs2484713607 · VCV2025763

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ehlers-Danlos syndrome, classic type, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 25 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.62	GERP 0.43, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL1A2
Protein: p.Pro477fs
Coding: c.1430del
MANE Select: NM_000089
dbSNP: rs2484713607
Type: Deletion
Location: chr7:94412608 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 477: 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.Pro477Leu Uncertain significance ★★ ⚠ same residue
COL1A2 c.432+4_432+7del Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.487-4_501del Pathogenic ★★ same condition
COL1A2 p.Gly286fs Pathogenic ★★ same condition
COL1A2 p.Pro1092fs Pathogenic ★★ same condition
COL1A2 p.Tyr1178_Asp1181del Uncertain significance ★★ same condition
COL1A2 c.2134-14del Likely benign ★★ same condition
COL1A2 c.640-10_640-9del 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-pro477fs (accessed [today's date]).

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