Is VWF p.Ser130= (c.390C>T) pathogenic?

VWF p.Ser130= (c.390C>T) is classified Benign/Likely benign in VWF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2022-06-03). Common (popmax 18.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with von Willebrand disease 2.

What condition is associated with VWF p.Ser130= (c.390C>T)?

VWF p.Ser130= (c.390C>T) is associated with von Willebrand disease 2, von Willebrand disease 1, von Willebrand disease 3 (ClinVar).

How is Von Willebrand disease inherited?

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

VWF p.Ser130=

Q: How common is VWF p.Ser130= (c.390C>T) in the general population?

VWF p.Ser130= (c.390C>T) is common (popmax 18.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.390C>T · rs2229444 · VCV256676

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 18.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

von Willebrand disease 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	phastCons 1
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.8% East Asian · 8,429/44,876 alleles

Filtering AF 18.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 0.932% 15,041/1,614,116 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	18.8%	5
African / African-American	2.13%	47
Remaining individualsnot grpmax-eligible	1%	100
Finnishnot grpmax-eligible	0.829%	121
South Asian	0.787%	127
Admixed American	0.765%	131
Middle Eastern	0.412%	242
European (non-Finnish)	0.223%	449
Ashkenazi Jewishnot grpmax-eligible	0.0979%	1,021

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.Ser130=
Coding: c.390C>T
MANE Select: NM_000552
dbSNP: rs2229444
Type: single nucleotide variant
Location: chr12:6110516 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 130: a β-strand; the vwfd 1 domain; a disulfide bond

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-ser130 (accessed [today's date]).

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