Is COL5A2 p.Pro962fs (c.2885del) pathogenic?

COL5A2 p.Pro962fs (c.2885del) is classified Likely pathogenic in COL5A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). Associated with Ehlers-Danlos syndrome, classic type, 2.

What condition is associated with COL5A2 p.Pro962fs (c.2885del)?

COL5A2 p.Pro962fs (c.2885del) is associated with Ehlers-Danlos syndrome, classic type, 2 (ClinVar).

How is Classical Ehlers-Danlos syndrome inherited?

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

COL5A2 p.Pro962fs

c.2885del · VCV4855549

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Ehlers-Danlos syndrome, classic type, 2

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 42 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -3, phastCons 0.16

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

Variant & gene context

Gene: COL5A2
Protein: p.Pro962fs
Coding: c.2885del
MANE Select: NM_000393
Type: Deletion
Location: chr2:189051366 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.15
Residue 962: the 'disordered' region

Full COL5A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, classic type, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Classical Ehlers-Danlos syndrome (Orphanet):

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

Similar variants

COL5A2 p.Pro962Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
COL5A2 c.2086-12del Benign ★★ same condition
COL5A2 c.2770-15del Benign/Likely benign ★★ same condition
COL5A2 c.3525+9del Likely benign ★★ same condition
COL5A2 c.4114-18_4114-17del Likely benign ★★ same condition
COL5A2 c.961-3del Benign/Likely benign ★★ same condition
COL5A2 p.Pro962Thr Likely benign ★★ same residue
COL5A2 c.568-316_3525+41del 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/col5a2-p-pro962fs (accessed [today's date]).

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