Is VWF p.Arg447fs (c.1339del) pathogenic?

VWF p.Arg447fs (c.1339del) is classified Likely pathogenic in VWF (ClinVar, Single submitter, 2 submitters; last evaluated 2019-02-01). Absent from gnomAD; Associated with hereditary von Willebrand disease.

What condition is associated with VWF p.Arg447fs (c.1339del)?

VWF p.Arg447fs (c.1339del) is associated with hereditary von Willebrand disease (ClinVar).

How common is VWF p.Arg447fs (c.1339del) in the general population?

VWF p.Arg447fs (c.1339del) is absent from gnomAD (gnomAD).

How is Von Willebrand disease inherited?

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

VWF p.Arg447fs

c.1339del · rs1591895308 · VCV626925

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary von Willebrand disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	phastCons 1

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: VWF
Protein: p.Arg447fs
Coding: c.1339del
MANE Select: NM_000552
dbSNP: rs1591895308
Type: Deletion
Location: chr12:6064339 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 447: a β-strand; the vwfd 2 domain; a disulfide bond

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

Disease context

hereditary von Willebrand disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Von Willebrand disease (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

VWF p.Ile1535_Val1537del Likely pathogenic ★★ same condition
VWF p.Pro812fs Pathogenic ★★ same condition
VWF p.Arg447Trp Uncertain significance ★★ same residue
VWF c.221-10_532+52del Pathogenic ★ same condition
VWF c.221-6_532+30del Likely pathogenic ★ same condition
VWF c.5621-47_5842+51del Pathogenic ★ same condition
VWF c.5621-50_5842+50del Pathogenic ★ same condition
VWF p.Asp437_Arg442del 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/vwf-p-arg447fs (accessed [today's date]).

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