VWF p.Ser489=
c.1467C>T · rs377066810 · VCV806807
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -8.7 | GERP -5 |
| Overall | ||
| CADD | 0.446 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,018 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000868%
14/1,613,664 alleles · very rare
exomes 14/1,461,358 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,006 |
| East Asian | 0.00223% | 44,884 |
| South Asian | 0.0022% | 45,538 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| African / African-American | 0.00133% | 75,042 |
| European (non-Finnish) | 0.000508% | 196,670 |
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.Ser489=
- Coding
- c.1467C>T
- MANE Select
- NM_000552
- dbSNP
- rs377066810
- Type
- single nucleotide variant
- Location
- chr12:6063020 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Residue 489
- the vwfd 2 domain
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-ser489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown