Is VWF p.Ser71Ter (c.212C>A) pathogenic?

VWF p.Ser71Ter (c.212C>A) is classified Likely pathogenic in VWF (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-20). Absent from gnomAD v4.1; Associated with von Willebrand disease 3.

What condition is associated with VWF p.Ser71Ter (c.212C>A)?

VWF p.Ser71Ter (c.212C>A) is associated with von Willebrand disease 3 (ClinVar).

How common is VWF p.Ser71Ter (c.212C>A) in the general population?

VWF p.Ser71Ter (c.212C>A) is absent from gnomAD v4.1 (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.Ser71Ter

c.212C>A · rs62643619 · VCV100204

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

von Willebrand disease 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 52
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VWF
Protein: p.Ser71Ter
Coding: c.212C>A
MANE Select: NM_000552
dbSNP: rs62643619
Type: single nucleotide variant
Location: chr12:6121182 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 71: a β-strand; the vwfd 1 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.Ser71Leu Uncertain significance ★ same residue
VWF p.Ser71= Likely benign ★ same residue
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-ser71ter (accessed [today's date]).

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