Is VWF p.Ser673fs (c.2018_2019del) pathogenic?

VWF p.Ser673fs (c.20182019del) is classified Pathogenic in VWF (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-29). Very rare (popmax 8.47e-05%, nfe); Associated with von Willebrand disease 3.

What condition is associated with VWF p.Ser673fs (c.2018_2019del)?

VWF p.Ser673fs (c.2018_2019del) is associated with von Willebrand disease 3 (ClinVar).

How common is VWF p.Ser673fs (c.2018_2019del) in the general population?

VWF p.Ser673fs (c.2018_2019del) is very rare (popmax 8.47e-05%, nfe) (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.Ser673fs

c.2018_2019del · rs61748462 · VCV1065252

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

von Willebrand disease 3

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 16 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.086	GERP -4.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.2e-05% 1/1,614,120 alleles · very rare exomes 1/1,461,876 · genomes 0/152,244 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: VWF
Protein: p.Ser673fs
Coding: c.2018_2019del
MANE Select: NM_000552
dbSNP: rs61748462
Type: Microsatellite
Location: chr12:6052710 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 673: the til 2 domain

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

Disease context

von Willebrand disease 3 — 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.Cys2418fs Pathogenic ★ same condition
VWF p.Cys255fs Pathogenic same condition
VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same condition
VWF p.Arg1659Ter Pathogenic ★★★ same condition
VWF p.Arg324Ter Pathogenic ★★★ same condition
VWF p.Arg760Cys Likely pathogenic ★★★ same condition
VWF p.Arg816Trp Pathogenic ★★★ ⚠ same condition
VWF p.Arg854Gln 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-ser673fs (accessed [today's date]).

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