Is VWF p.Ser2479= (c.7437G>A) pathogenic?

VWF p.Ser2479= (c.7437G>A) is classified Pathogenic in VWF (ClinVar, No assertion criteria, 2 submitters). Very rare (popmax 0.00446%, eas); Associated with hereditary von Willebrand disease.

What condition is associated with VWF p.Ser2479= (c.7437G>A)?

VWF p.Ser2479= (c.7437G>A) is associated with hereditary von Willebrand disease (ClinVar).

How common is VWF p.Ser2479= (c.7437G>A) in the general population?

VWF p.Ser2479= (c.7437G>A) is very rare (popmax 0.00446%, 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.Ser2479=

c.7437G>A · rs267607363 · VCV100473

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

hereditary von Willebrand disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.79	donor gain · deltas
Pangolin	Δ0.79	gain · loss 0.79 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.7	GERP 0.53, phastCons 0.93
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,868 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000744% 12/1,613,638 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,434
South Asian	0.00329%	30,359
African / African-American	0.00133%	74,920
European (non-Finnish)	0.000508%	196,670

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.Ser2479=
Coding: c.7437G>A
MANE Select: NM_000552
dbSNP: rs267607363
Type: single nucleotide variant
Location: chr12:5976111 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 2479: the vwfc 2 domain; a disulfide bond

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

Disease context

hereditary von Willebrand disease — 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.Ser2479Leu Uncertain significance ★ ⚠ same residue
VWF p.Ser2479Pro Likely benign ★ same residue
VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same condition
VWF p.Arg1308Cys Pathogenic ★★★ ⚠ same condition
VWF p.Arg1341Gln Pathogenic ★★★ ⚠ same condition
VWF p.Arg1374His Pathogenic ★★★ ⚠ same condition
VWF p.Arg1399Cys Pathogenic ★★★ same condition
VWF p.Arg1597Trp 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-ser2479 (accessed [today's date]).

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