VWF p.Pro1337=
c.4011G>A · rs1800381 · VCV1336765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 -1.8 | GERP -3.2 |
| Overall | ||
| CADD | 7.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,880 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00366%
59/1,613,958 alleles · very rare
exomes 55/1,461,614 · genomes 4/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,960 |
| Admixed American | 0.00666% | 15,007 |
| African / African-American | 0.004% | 25,019 |
| European (non-Finnish) | 0.00398% | 25,104 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,247 |
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.Pro1337=
- Coding
- c.4011G>A
- MANE Select
- NM_000552
- dbSNP
- rs1800381
- Type
- single nucleotide variant
- Location
- chr12:6019407 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Residue 1337
- the vwfa 1; binding site for platelet glycoprotein ib domain; an α-helix
Similar variants
- VWF p.Pro1337Leu Likely pathogenic ★★★ ⚠ same residue
- VWF p.Pro1337Gln Uncertain significance ★★★ same residue
- 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
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-pro1337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown