Is PKD2 p.Val466Phe (c.1396G>T) pathogenic?

PKD2 p.Val466Phe (c.1396G>T) is classified Uncertain significance in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely benign (0.172); Absent from gnomAD v4.1; Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Val466Phe (c.1396G>T)?

PKD2 p.Val466Phe (c.1396G>T) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Val466Phe (c.1396G>T) in the general population?

PKD2 p.Val466Phe (c.1396G>T) 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.

What do computational predictors say about PKD2 p.Val466Phe (c.1396G>T)?

AlphaMissense predicts likely benign (score 0.172) — an in-silico prediction, not a clinical call.

PKD2 p.Val466Phe

c.1396G>T · rs1395534748 · VCV2702095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.172 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.172	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -11.90	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -0.99, phastCons 1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val466Phe
Coding: c.1396G>T
MANE Select: NM_000297
dbSNP: rs1395534748
Type: single nucleotide variant
Location: chr4:88046718 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 466: the ph domain; a β-strand

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.Cys466Phe 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-val466phe (accessed [today's date]).

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