Is PKD2 p.Arg306Gln (c.917G>A) pathogenic?

PKD2 p.Arg306Gln (c.917G>A) is classified Uncertain significance in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). AlphaMissense: likely benign (0.0679); Very rare (popmax 0.00133%, afr); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Arg306Gln (c.917G>A)?

PKD2 p.Arg306Gln (c.917G>A) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Arg306Gln (c.917G>A) in the general population?

PKD2 p.Arg306Gln (c.917G>A) is very rare (popmax 0.00133%, afr) (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.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

PKD2 p.Arg306Gln

c.917G>A · rs990932947 · VCV1987951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.085, phastCons 1
Overall
CADD	18.88	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 0.00133% African / African-American · 1/75,032 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,828 alleles · very rare exomes 7/1,461,528 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,032
European (non-Finnish)	0.000509%	196,620

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_000297
dbSNP: rs990932947
Type: single nucleotide variant
Location: chr4:88038324 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB

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

PKD2 p.Arg306Ter Pathogenic ★★ same residue
PKD2 p.Arg306Gly Uncertain significance ★★ ⚠ same residue
PRKD2 p.Cys306= Benign ★★ 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

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-arg306gln (accessed [today's date]).

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