Is VWF p.Pro1480= (c.4440G>A) pathogenic?

VWF p.Pro1480= (c.4440G>A) is classified Likely benign in VWF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with VWF p.Pro1480= (c.4440G>A)?

VWF p.Pro1480= (c.4440G>A) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Pro1480= (c.4440G>A) in the general population?

VWF p.Pro1480= (c.4440G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

VWF p.Pro1480=

c.4440G>A · VCV3815615

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

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 -20	GERP -2.8
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,062 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000547% 8/1,461,658 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,531
African / African-American	0.00133%	75,002
European (non-Finnish)	0.000424%	235,970

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.Pro1480=
Coding: c.4440G>A
MANE Select: NM_000552
Type: single nucleotide variant
Location: chr12:6018978 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 1480: 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.Pro1480Leu 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-pro1480 (accessed [today's date]).

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