Is VHL p.Val83= (c.249C>A) pathogenic?

VHL p.Val83= (c.249C>A) is classified Likely benign in VHL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Absent from gnomAD v4.1; Associated with Chuvash polycythemia.

What condition is associated with VHL p.Val83= (c.249C>A)?

VHL p.Val83= (c.249C>A) is associated with Chuvash polycythemia, von Hippel-Lindau disease, hereditary neoplastic syndrome (ClinVar).

How common is VHL p.Val83= (c.249C>A) in the general population?

VHL p.Val83= (c.249C>A) is absent from gnomAD v4.1 (gnomAD).

How is Chuvash erythrocytosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

VHL p.Val83=

c.249C>A · rs1271292937 · VCV3232218

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Chuvash polycythemia

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 -0.47	GERP -3.4, phastCons 0.039
Overall
CADD	6.798	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.Val83=
Coding: c.249C>A
MANE Select: NM_000551
dbSNP: rs1271292937
Type: single nucleotide variant
Location: chr3:10142096 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 83: a UniProt-annotated variant site (in vhld)

Full VHL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Chuvash polycythemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: von Hippel-Lindau disease hereditary neoplastic syndrome

For Chuvash erythrocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

VHL p.Val83Leu Uncertain significance ★★ same residue
VHL p.Val83Ile Uncertain significance ★ ⚠ same residue
VHL p.Val83fs Pathogenic ★ 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-val83 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown