VWF p.Ala7=
c.21C>T · rs144128523 · VCV619740
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0527%, sas)
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 -4.6 | GERP -4.3 |
| Overall | ||
| CADD | 4.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0527%
South Asian · 48/91,090 alleles
Filtering AF
0.0408%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.0235%
379/1,614,058 alleles · ultra-rare
exomes 351/1,461,876 · genomes 28/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0527% | 1,898 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| European (non-Finnish) | 0.0248% | 4,027 |
| African / African-American | 0.0107% | 9,365 |
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.Ala7=
- Coding
- c.21C>T
- MANE Select
- NM_000552
- dbSNP
- rs144128523
- Type
- single nucleotide variant
- Location
- chr12:6123176 (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-ala7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown