Is VHL p.Pro103fs (c.305dup) pathogenic?

VHL p.Pro103fs (c.305dup) is classified Pathogenic in VHL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-19). No gnomAD frequency available for this variant; Associated with Chuvash polycythemia.

What condition is associated with VHL p.Pro103fs (c.305dup)?

VHL p.Pro103fs (c.305dup) is associated with Chuvash polycythemia, von Hippel-Lindau disease (ClinVar).

How common is VHL p.Pro103fs (c.305dup) in the general population?

VHL p.Pro103fs (c.305dup) is no gnomAD frequency available for this variant (gnomAD).

How is Chuvash erythrocytosis inherited?

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

VHL p.Pro103fs

c.305dup · rs1559426145 · VCV2943402

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Chuvash polycythemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 0.44, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Pro103fs
Coding: c.305dup
MANE Select: NM_000551
dbSNP: rs1559426145
Type: Duplication
Location: chr3:10142150 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 103: the 'involved in binding to cct complex' region

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

For Chuvash erythrocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

VHL p.Pro103= Benign/Likely benign ★★ same residue
VHL p.Pro103Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
VHL p.Pro103Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
VHL p.Pro103Ser Uncertain significance ★ ⚠ same residue
VHL p.Arg60fs Pathogenic ★★ same condition
VHL p.Arg64fs Pathogenic/Likely pathogenic ★★ same condition
VHL p.Arg69fs Pathogenic ★★ same condition
VHL p.Glu55fs 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-pro103fs (accessed [today's date]).

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