Is PKD2 p.Val880= (c.2640G>A) pathogenic?

PKD2 p.Val880= (c.2640G>A) is classified Uncertain significance in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). Absent from gnomAD v4.1; Associated with polycystic kidney disease 2.

What condition is associated with PKD2 p.Val880= (c.2640G>A)?

PKD2 p.Val880= (c.2640G>A) is associated with polycystic kidney disease 2 (ClinVar).

How common is PKD2 p.Val880= (c.2640G>A) in the general population?

PKD2 p.Val880= (c.2640G>A) is absent from gnomAD v4.1 (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.Val880=

c.2640G>A · VCV3774562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

polycystic kidney disease 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.85	donor gain, 3 bp away · masked 0 · deltas
Pangolin	Δ0.69	gain · loss 0.50 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3	GERP 0.54, phastCons 1
Overall
CADD	19.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PKD2
Protein: p.Val880=
Coding: c.2640G>A
MANE Select: NM_000297
Type: single nucleotide variant
Location: chr4:88074929 (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 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
PKD2 c.1898+5G>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-val880 (accessed [today's date]).

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