Is PKD2 p.Asp511fs (c.1532_1533insAT) pathogenic?

PKD2 p.Asp511fs (c.15321533insAT) is classified Pathogenic in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Associated with polycystic kidney disease 2.

What condition is associated with PKD2 p.Asp511fs (c.1532_1533insAT)?

PKD2 p.Asp511fs (c.1532_1533insAT) is associated with polycystic kidney disease 2 (ClinVar).

How is Autosomal dominant polycystic kidney disease inherited?

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

PKD2 p.Asp511fs

c.1532_1533insAT · VCV4687837

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

polycystic kidney disease 2

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: PKD2
Protein: p.Asp511fs
Coding: c.1532_1533insAT
MANE Select: NM_000297
Type: Insertion
Location: chr4:88046854 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB

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

Disease context

polycystic kidney disease 2 — 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.Asp511Val Pathogenic same residue
PKD2 c.2241-2_2241-1insTT Likely pathogenic ★ same condition
PKD2 p.His750fs Likely pathogenic ★ same condition
PKD2 p.Phe574fs Pathogenic ★ same condition
PKD2 p.Ser802fs Pathogenic ★ same condition
PKD2 c.1094+1G>A Pathogenic ★★ same condition
PKD2 c.1094+1G>C Pathogenic ★★ same condition
PKD2 c.1094+3_1094+6del 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-asp511fs (accessed [today's date]).

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