Is VHL p.Pro102= (c.306G>T) pathogenic?

VHL p.Pro102= (c.306G>T) is classified Benign/Likely benign in VHL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.000339%, nfe); Associated with von Hippel-Lindau disease.

What condition is associated with VHL p.Pro102= (c.306G>T)?

VHL p.Pro102= (c.306G>T) is associated with von Hippel-Lindau disease, Chuvash polycythemia, hereditary neoplastic syndrome (ClinVar).

How common is VHL p.Pro102= (c.306G>T) in the general population?

VHL p.Pro102= (c.306G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Von Hippel-Lindau disease inherited?

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

VHL p.Pro102=

c.306G>T · rs550155859 · VCV1103013

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 0.018	GERP -0.78
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,492 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00025% 4/1,598,884 alleles · very rare exomes 4/1,446,644 · genomes 0/152,240 · joint denominator

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: VHL
Protein: p.Pro102=
Coding: c.306G>T
MANE Select: NM_000551
dbSNP: rs550155859
Type: single nucleotide variant
Location: chr3:10142153 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 102: the 'involved in binding to cct complex' region

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 hereditary neoplastic syndrome

For Von Hippel-Lindau disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

VHL p.Pro102Leu Uncertain significance ★★ ⚠ same residue
VHL p.Pro102Arg Uncertain significance ★ ⚠ same residue
VHL p.Pro102Gln Uncertain significance ★ ⚠ same residue
VHL p.Pro102Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
VHL p.Pro102Thr Uncertain significance ★ ⚠ same residue
VHL p.Arg64Pro Pathogenic ★★★ same condition
VHL p.Asn78Ser Pathogenic ★★★ ⚠ same condition
VHL p.Glu70Ter 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-pro102 (accessed [today's date]).

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