Is VWF p.Pro296Ala (c.886C>G) pathogenic?

VWF p.Pro296Ala (c.886C>G) is classified Uncertain significance in VWF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1393); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with VWF p.Pro296Ala (c.886C>G)?

VWF p.Pro296Ala (c.886C>G) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Pro296Ala (c.886C>G) in the general population?

VWF p.Pro296Ala (c.886C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VWF p.Pro296Ala (c.886C>G)?

AlphaMissense predicts likely benign (score 0.1393) — an in-silico prediction, not a clinical call.

VWF p.Pro296Ala

c.886C>G · VCV4200033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1393 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1393	likely benign
REVEL	0.785	moderately pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 97 kb · p 0.18 · regional, not allelic
Overall
CADD	25.1	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.Pro296Ala
Coding: c.886C>G
MANE Select: NM_000552
Type: single nucleotide variant
Location: chr12:6073730 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 296: a β-strand; the til 1 domain; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VWF p.Pro296Leu Uncertain significance ★ ⚠ same residue
VWF p.Glu383Ter Pathogenic ★★ same condition
VWF p.Ala1207Ser Uncertain significance ★★ ⚠ same condition
VWF p.Ala1420Thr Uncertain significance ★★ same condition
VWF p.Ala2155Ser Uncertain significance ★★ ⚠ same condition
VWF p.Ala465Pro Uncertain significance ★★ same condition
VWF p.Ala54Val Uncertain significance ★★ ⚠ same condition
VWF p.Arg1342His Uncertain significance ★★ ⚠ 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-pro296ala (accessed [today's date]).

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