Is PKD2 p.Pro173= (c.519G>A) pathogenic?

PKD2 p.Pro173= (c.519G>A) is classified Likely benign in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). Very rare (popmax 0.00495%, nfe); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Pro173= (c.519G>A)?

PKD2 p.Pro173= (c.519G>A) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Pro173= (c.519G>A) in the general population?

PKD2 p.Pro173= (c.519G>A) is very rare (popmax 0.00495%, nfe) (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.Pro173=

c.519G>A · rs762929169 · VCV1921308

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00495%, nfe)

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 1.3	GERP -1.8, phastCons 1
Overall
CADD	13.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00495% European (non-Finnish) · 55/1,110,874 alleles

Filtering AF 0.00389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00349%

Overall 0.00411% 60/1,461,088 alleles · very rare exomes 59/1,309,082 · genomes 1/152,006 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00709%	14,096
European (non-Finnish)grpmax	0.00495%	20,198
East Asian	0.00294%	33,956

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro173=
Coding: c.519G>A
MANE Select: NM_000297
dbSNP: rs762929169
Type: single nucleotide variant
Location: chr4:88008252 (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

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

PRKD2 p.Gly173Arg 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
PKD2 c.2118+1G>C 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-pro173 (accessed [today's date]).

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