Is VHL p.Ser80= (c.240T>C) pathogenic?

VHL p.Ser80= (c.240T>C) is classified Benign/Likely benign in VHL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-07). Absent from gnomAD v4.1; Associated with Chuvash polycythemia.

What condition is associated with VHL p.Ser80= (c.240T>C)?

VHL p.Ser80= (c.240T>C) is associated with Chuvash polycythemia, von Hippel-Lindau disease, hereditary neoplastic syndrome (ClinVar).

How common is VHL p.Ser80= (c.240T>C) in the general population?

VHL p.Ser80= (c.240T>C) 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.Ser80=

c.240T>C · rs1553619424 · VCV526699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 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 -0.2	GERP -1.9, phastCons 0.38
Overall
CADD	12.93	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.Ser80=
Coding: c.240T>C
MANE Select: NM_000551
dbSNP: rs1553619424
Type: single nucleotide variant
Location: chr3:10142087 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 80: a β-strand; a UniProt-annotated variant site (in vhld; type i); a UniProt-annotated variant site (in pcc and vhld; type i)

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.Ser80Arg Likely pathogenic ★★ same residue
VHL p.Ser80Asn Pathogenic/Likely pathogenic ★★ same residue
VHL p.Ser80Gly Pathogenic/Likely pathogenic ★★ same residue
VHL p.Ser80Ile Pathogenic/Likely pathogenic ★★ same residue
VHL p.Ser80Thr Uncertain significance ★ ⚠ same residue
VHL p.Ser80fs Pathogenic ★ same residue
VHL p.Ser80_Arg82del Uncertain significance ★ same residue
VHL p.Arg64Pro 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-ser80 (accessed [today's date]).

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