Is VWF p.Ser394= (c.1182A>C) pathogenic?

VWF p.Ser394= (c.1182A>C) is classified Benign/Likely benign in VWF (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-12). Common (popmax 50.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with von Willebrand disease 2.

What condition is associated with VWF p.Ser394= (c.1182A>C)?

VWF p.Ser394= (c.1182A>C) 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.Ser394=

Q: How common is VWF p.Ser394= (c.1182A>C) in the general population?

VWF p.Ser394= (c.1182A>C) is common (popmax 50.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1182A>C · rs1800376 · VCV256651

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 50.1%, afr) — 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 1.1	phastCons 1
Overall
CADD	7.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.1% African / African-American · 37,475/74,758 alleles

Filtering AF 49.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.5%

Overall 15.8% 254,635/1,613,308 alleles · common exomes 218,684/1,461,448 · genomes 35,951/151,860 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	50.1%	2
South Asian	24%	4
East Asian	21.6%	5
Middle Eastern	17.6%	6
Remaining individualsnot grpmax-eligible	17%	6
European (non-Finnish)	13.4%	7
Finnishnot grpmax-eligible	10.5%	9
Admixed American	10.4%	10
Ashkenazi Jewishnot grpmax-eligible	8.86%	11
Amishnot grpmax-eligible	7.25%	14

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.Ser394=
Coding: c.1182A>C
MANE Select: NM_000552
dbSNP: rs1800376
Type: single nucleotide variant
Location: chr12:6065248 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 394: a turn; the vwfd 2 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.Ser394Ter Likely pathogenic ★ same residue
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

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-ser394 (accessed [today's date]).

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