Is PKD2 p.Val233= (c.699C>T) pathogenic?

PKD2 p.Val233= (c.699C>T) is classified Benign in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Ultra-rare (popmax 0.0399%, afr); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Val233= (c.699C>T)?

PKD2 p.Val233= (c.699C>T) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Val233= (c.699C>T) in the general population?

PKD2 p.Val233= (c.699C>T) is ultra-rare (popmax 0.0399%, afr) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

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

PKD2 p.Val233=

c.699C>T · rs753107440 · VCV2195138

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0399%, afr)

Conditions

autosomal dominant polycystic kidney 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 1.1	GERP -0.19, phastCons 0.58
Overall
CADD	8.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0399% African / African-American · 29/72,768 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00206% 31/1,504,514 alleles · ultra-rare exomes 11/1,352,440 · genomes 20/152,074 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0399%	2,509
Remaining individualsnot grpmax-eligible	0.0034%	29,448

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: PKD2
Protein: p.Val233=
Coding: c.699C>T
MANE Select: NM_000297
dbSNP: rs753107440
Type: single nucleotide variant
Location: chr4:88019561 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 233: the 'disordered' region

Full PKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant polycystic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PKD2 p.Val233Ile Uncertain significance ★★ ⚠ same residue
PRKD2 p.Arg233His Uncertain significance ★ ⚠ same residue
PKD2 c.1094+1G>A Pathogenic ★★ same condition
PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1898+5G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.2019+1G>A Pathogenic ★★ same condition
PKD2 c.2020-2A>G Likely 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/pkd2-p-val233 (accessed [today's date]).

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