VWF p.Pro744=
c.2232C>T · VCV3768850
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00568%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00568%
European (non-Finnish) · 67/1,180,018 alleles
Filtering AF
0.00453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00483%
78/1,614,098 alleles · very rare
exomes 72/1,461,786 · genomes 6/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00568% | 17,612 |
| African / African-American | 0.00533% | 18,764 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0022% | 45,541 |
| Admixed American | 0.00167% | 60,024 |
| Finnishnot grpmax-eligible | 0.00156% | 63,950 |
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.Pro744=
- Coding
- c.2232C>T
- MANE Select
- NM_000552
- Type
- single nucleotide variant
- Location
- chr12:6046772 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
Similar variants
- VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same type
- VWF p.Arg1308Cys Pathogenic ★★★ ⚠ same type
- VWF p.Arg1315His Likely pathogenic ★★★ ⚠ same type
- VWF p.Arg1315Leu Likely pathogenic ★★★ same type
- VWF p.Arg1334Trp Likely pathogenic ★★★ ⚠ same type
- VWF p.Arg1341Gln Pathogenic ★★★ ⚠ same type
- VWF p.Arg1341Trp Pathogenic ★★★ ⚠ same type
- VWF p.Arg1374His Pathogenic ★★★ ⚠ same type
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-pro744 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown