VHL p.Val66=
c.198G>A · rs2125124972 · VCV2953643
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
von Hippel-Lindau disease
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 12.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- VHL
- Protein
- p.Val66=
- Coding
- c.198G>A
- MANE Select
- NM_000551
- dbSNP
- rs2125124972
- Type
- single nucleotide variant
- Location
- chr3:10142045 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.45 · 143 PDB
- Residue 66
- a UniProt-annotated variant site (in vhld; type i)
Disease context
von Hippel-Lindau disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Chuvash polycythemia
For Von Hippel-Lindau disease (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-9 / 100 000 (United Kingdom)
Similar variants
- VHL p.Val66Ala Likely benign ★ same residue
- VHL p.Val66Glu Likely benign ★ same residue
- VHL p.Val66Met Likely benign ★ same residue
- VHL p.Arg64Pro Pathogenic ★★★ same condition
- VHL p.Asn78Ser Pathogenic ★★★ ⚠ same condition
- VHL p.Glu70Ter Pathogenic ★★★ same condition
- VHL p.Pro86Leu Pathogenic ★★★ same condition
- VHL p.Ser65Trp Pathogenic ★★★ same condition
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/vhl-p-val66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown