Is VHL p.Ser68= (c.204G>T) pathogenic?

VHL p.Ser68= (c.204G>T) is classified Likely benign in VHL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-08). No allele count reported in gnomAD v4.1 (AN 1,605,432); Associated with von Hippel-Lindau disease.

What condition is associated with VHL p.Ser68= (c.204G>T)?

VHL p.Ser68= (c.204G>T) is associated with von Hippel-Lindau disease, Chuvash polycythemia (ClinVar).

How common is VHL p.Ser68= (c.204G>T) in the general population?

VHL p.Ser68= (c.204G>T) is no allele count reported in gnomAD v4.1 (AN 1,605,432) (gnomAD).

How is Von Hippel-Lindau disease inherited?

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

VHL p.Ser68=

c.204G>T · rs773246608 · VCV1538707

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,432)

Conditions

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 -0.37	GERP -3.4, phastCons 0.01
Overall
CADD	8.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,432). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: VHL
Protein: p.Ser68=
Coding: c.204G>T
MANE Select: NM_000551
dbSNP: rs773246608
Type: single nucleotide variant
Location: chr3:10142051 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 68: a UniProt-annotated variant site (in vhld; type i); a UniProt-annotated variant site (in pcc and vhld; type ii)

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

Disease context

von Hippel-Lindau disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also 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.Ser68Ter Pathogenic ★★ same residue
VHL p.Ser68Pro Pathogenic ★ same residue
VHL p.Ser68Leu Conflicting classifications of pathogenicity ★ ⚠ 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-ser68 (accessed [today's date]).

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