Is PKD2 p.Pro261= (c.783C>T) pathogenic?

PKD2 p.Pro261= (c.783C>T) is classified Likely benign in PKD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-25). Ultra-rare (popmax 0.0164%, mid); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Pro261= (c.783C>T)?

PKD2 p.Pro261= (c.783C>T) is associated with autosomal dominant polycystic kidney disease, polycystic kidney disease 2 (ClinVar).

How common is PKD2 p.Pro261= (c.783C>T) in the general population?

PKD2 p.Pro261= (c.783C>T) is ultra-rare (popmax 0.0164%, mid) (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.Pro261=

c.783C>T · rs766343471 · VCV1111461

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -9.7	GERP -3.8
Overall
CADD	0.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00174% 28/1,613,796 alleles · ultra-rare exomes 26/1,461,654 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.00329%	30,360
European (non-Finnish)	0.00186%	53,629
Admixed American	0.00167%	59,994
African / African-American	0.00134%	74,900

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.Pro261=
Coding: c.783C>T
MANE Select: NM_000297
dbSNP: rs766343471
Type: single nucleotide variant
Location: chr4:88036293 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB

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

Also linked: polycystic kidney disease 2

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

PKD2 p.Pro261Ser Uncertain significance ★ ⚠ same residue
PKD2 c.1094+1G>A Pathogenic ★★ same condition
PKD2 c.1094+1G>C Pathogenic ★★ same condition
PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1320-2A>C Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1549-1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1716+2T>A Pathogenic/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-pro261 (accessed [today's date]).

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