Is PKD2 p.Phe666fs (c.1998_2001del) pathogenic?

PKD2 p.Phe666fs (c.19982001del) is classified Pathogenic in PKD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-10-12). No gnomAD frequency available for this variant; Associated with polycystic kidney disease 2.

What condition is associated with PKD2 p.Phe666fs (c.1998_2001del)?

PKD2 p.Phe666fs (c.1998_2001del) is associated with polycystic kidney disease 2, polycystic kidney disease (ClinVar).

How common is PKD2 p.Phe666fs (c.1998_2001del) in the general population?

PKD2 p.Phe666fs (c.1998_2001del) is no gnomAD frequency available for this variant (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.Phe666fs

c.1998_2001del · rs1720431219 · VCV997110

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2.5	GERP -1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PKD2
Protein: p.Phe666fs
Coding: c.1998_2001del
MANE Select: NM_000297
dbSNP: rs1720431219
Type: Deletion
Location: chr4:88058080 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 666: the protein kinase domain

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

Also linked: polycystic kidney disease

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

PKD2 c.1094+3_1094+6del Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.1320-2del Pathogenic ★★ same condition
PKD2 c.2020-1_2020del Pathogenic/Likely pathogenic ★★ same condition
PKD2 c.596-12_599del Pathogenic ★★ same condition
PKD2 p.Asn737fs Pathogenic ★★ same condition
PKD2 p.Gly833fs Pathogenic ★★ same condition
PKD2 p.Leu231fs Pathogenic/Likely pathogenic ★★ same condition
PKD2 p.Leu842_Val843insTer 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-phe666fs (accessed [today's date]).

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