Is PKD2 p.Phe482Val (c.1444T>G) pathogenic?

PKD2 p.Phe482Val (c.1444T>G) is classified Uncertain significance in PKD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0669); Ultra-rare (popmax 0.0165%, mid); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Phe482Val (c.1444T>G)?

PKD2 p.Phe482Val (c.1444T>G) is associated with autosomal dominant polycystic kidney disease, polycystic kidney disease 2 (ClinVar).

How common is PKD2 p.Phe482Val (c.1444T>G) in the general population?

PKD2 p.Phe482Val (c.1444T>G) is ultra-rare (popmax 0.0165%, mid) (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.Phe482Val (c.1444T>G)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

PKD2 p.Phe482Val

c.1444T>G · rs201504575 · VCV633687

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -3.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -1.3, phastCons 0.93
Overall
CADD	16.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,050 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00242% 39/1,611,914 alleles · ultra-rare exomes 31/1,459,554 · genomes 8/152,360 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
Admixed American	0.01%	10,004
Remaining individualsnot grpmax-eligible	0.00961%	10,409
European (non-Finnish)	0.00212%	47,117
African / African-American	0.00133%	75,016

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PKD2
Protein: p.Phe482Val
Coding: c.1444T>G
MANE Select: NM_000297
dbSNP: rs201504575
Type: single nucleotide variant
Location: chr4:88046766 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 482: the ph domain

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

Also linked: polycystic kidney disease 2

For Autosomal dominant polycystic kidney disease (Orphanet):

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

Similar variants

PKD2 p.Phe482Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PKD2 p.Phe482_Tyr486del Uncertain significance ★ same residue
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

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-phe482val (accessed [today's date]).

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