Is VWF p.Ser1285Pro (c.3853T>C) pathogenic?

VWF p.Ser1285Pro (c.3853T>C) is classified Pathogenic in VWF (ClinVar, Single submitter, 2 submitters; last evaluated 2021-01-21). AlphaMissense: likely pathogenic (0.9657); Absent from gnomAD v4.1; Associated with von Willebrand disease 2.

What condition is associated with VWF p.Ser1285Pro (c.3853T>C)?

VWF p.Ser1285Pro (c.3853T>C) is associated with von Willebrand disease 2 (ClinVar).

How common is VWF p.Ser1285Pro (c.3853T>C) in the general population?

VWF p.Ser1285Pro (c.3853T>C) 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.

What do computational predictors say about VWF p.Ser1285Pro (c.3853T>C)?

AlphaMissense predicts likely pathogenic (score 0.9657) — an in-silico prediction, not a clinical call.

VWF p.Ser1285Pro

c.3853T>C · rs61749379 · VCV100292

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9657 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

von Willebrand disease 2

Computational evidence

Protein change
AlphaMissense	0.9657	likely pathogenic ✓ concordant with ClinVar · top 2% in VWF
REVEL	0.966	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 30 kb · p 3e-21 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser1285Pro
Coding: c.3853T>C
MANE Select: NM_000552
dbSNP: rs61749379
Type: single nucleotide variant
Location: chr12:6019565 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 1285: the vwfa 1; binding site for platelet glycoprotein ib domain; a β-strand; 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

For Von Willebrand disease (Orphanet):

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

Similar variants

VWF p.Ser1285Ala Likely pathogenic ★ same residue
VWF p.Ser1285Phe 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

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-ser1285pro (accessed [today's date]).

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