Is PKD2 p.Phe503fs (c.1508del) pathogenic?

PKD2 p.Phe503fs (c.1508del) is classified Likely pathogenic in PKD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-10). No gnomAD frequency available for this variant; Associated with PKD2-related disorder.

What condition is associated with PKD2 p.Phe503fs (c.1508del)?

PKD2 p.Phe503fs (c.1508del) is associated with PKD2-related disorder (ClinVar).

How common is PKD2 p.Phe503fs (c.1508del) in the general population?

PKD2 p.Phe503fs (c.1508del) is no gnomAD frequency available for this variant (gnomAD).

PKD2 p.Phe503fs

c.1508del · rs2475925677 · VCV3031001

Likely pathogenic Single submitter

Classification

Likely 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

PKD2-related disorder

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 9.3	GERP 1.9, 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.Phe503fs
Coding: c.1508del
MANE Select: NM_000297
dbSNP: rs2475925677
Type: Deletion
Location: chr4:88046828 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 503: the ph domain; an α-helix

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

Disease context

PKD2-related disorder

Similar variants

PKD2 c.2020-1_2020del Pathogenic/Likely pathogenic ★★ same condition
PKD2 p.Asn737fs Pathogenic ★★ same condition
PKD2 p.Phe558fs Pathogenic ★★ same condition
PKD2 p.Ser518fs Pathogenic ★★ same condition
PKD2 p.Gly381fs Pathogenic ★ same condition
PKD2 p.His498fs Likely pathogenic ★ same condition
PKD2 p.Leu231_Ile232insTer Likely pathogenic ★ same condition
PKD2 p.Lys342fs 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-phe503fs (accessed [today's date]).

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