Is VWF p.Arg34Ter (c.100C>T) pathogenic?

VWF p.Arg34Ter (c.100C>T) is classified Pathogenic in VWF (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-10). Very rare (popmax 0.00223%, eas); Associated with von Willebrand disease 2.

What condition is associated with VWF p.Arg34Ter (c.100C>T)?

VWF p.Arg34Ter (c.100C>T) is associated with von Willebrand disease 2, von Willebrand disease 1, von Willebrand disease 3 (ClinVar).

How common is VWF p.Arg34Ter (c.100C>T) in the general population?

VWF p.Arg34Ter (c.100C>T) is very rare (popmax 0.00223%, eas) (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.Arg34Ter

c.100C>T · rs61753984 · VCV100171

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

von Willebrand disease 2

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 4.2	GERP 1.3, phastCons 1
Overall
CADD	37.0	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

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000743% 12/1,614,210 alleles · very rare exomes 12/1,461,876 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,512
South Asian	0.0011%	91,082
European (non-Finnish)	0.000763%	131,115

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.Arg34Ter
Coding: c.100C>T
MANE Select: NM_000552
dbSNP: rs61753984
Type: single nucleotide variant
Location: chr12:6121294 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 34: 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 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: von Willebrand disease 1 von Willebrand disease 3

For Von Willebrand disease (Orphanet):

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

Similar variants

VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same condition
VWF p.Arg1308Cys Pathogenic ★★★ ⚠ same condition
VWF p.Arg1315His Likely pathogenic ★★★ ⚠ same condition
VWF p.Arg1315Leu Likely pathogenic ★★★ same condition
VWF p.Arg1341Gln Pathogenic ★★★ ⚠ same condition
VWF p.Arg1341Trp Pathogenic ★★★ ⚠ same condition
VWF p.Arg1374His Pathogenic ★★★ ⚠ same condition
VWF p.Arg1399Cys 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-arg34ter (accessed [today's date]).

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