Is VHL p.Pro71= (c.213C>T) pathogenic?

VHL p.Pro71= (c.213C>T) is classified Benign/Likely benign in VHL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0882%, sas); Associated with Chuvash polycythemia.

What condition is associated with VHL p.Pro71= (c.213C>T)?

VHL p.Pro71= (c.213C>T) is associated with Chuvash polycythemia, von Hippel-Lindau disease, hereditary neoplastic syndrome (ClinVar).

How common is VHL p.Pro71= (c.213C>T) in the general population?

VHL p.Pro71= (c.213C>T) is ultra-rare (popmax 0.0882%, sas) (gnomAD).

How is Chuvash erythrocytosis inherited?

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

VHL p.Pro71=

c.213C>T · rs201663073 · VCV215766

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0882%, sas)

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 -3, phastCons 0.96
Overall
CADD	13.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0882% South Asian · 80/90,686 alleles

Filtering AF 0.0726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0669%

Overall 0.00691% 111/1,607,260 alleles · ultra-rare exomes 99/1,454,906 · genomes 12/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0882%	1,134
Middle Eastern	0.0331%	3,025
East Asian	0.0246%	4,071
Remaining individualsnot grpmax-eligible	0.0192%	5,196
African / African-American	0.00533%	18,753
European (non-Finnish)	0.00017%	589,511

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.Pro71=
Coding: c.213C>T
MANE Select: NM_000551
dbSNP: rs201663073
Type: single nucleotide variant
Location: chr3:10142060 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 143 PDB
Residue 71: a β-strand; a UniProt-annotated variant site (in 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.Pro71Ser Uncertain significance ★★ ⚠ same residue
VHL p.Pro71Thr Uncertain significance ★ ⚠ same residue
VHL p.Pro71fs Pathogenic ★ same residue
VHL p.Pro71Leu Uncertain significance ★ ⚠ 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

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-pro71 (accessed [today's date]).

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