VWF p.Pro675=
c.2025G>A · rs779045480 · VCV310077
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.95 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.58 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP 2.3, phastCons 0.99 |
| Overall | ||
| CADD | 24.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00578%
Overall
0.0044%
71/1,614,076 alleles · ultra-rare
exomes 68/1,461,882 · genomes 3/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.015% | 6,667 |
| European (non-Finnish) | 0.00483% | 20,702 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| African / African-American | 0.00267% | 37,461 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
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.Pro675=
- Coding
- c.2025G>A
- MANE Select
- NM_000552
- dbSNP
- rs779045480
- Type
- single nucleotide variant
- Location
- chr12:6052704 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Residue 675
- the til 2 domain
Similar variants
- VWF p.Pro675Leu Uncertain significance ★ ⚠ same residue
- VWF p.Pro675Thr 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-pro675 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown