Is PKD2 p.Ser795Pro (c.2383T>C) pathogenic?

PKD2 p.Ser795Pro (c.2383T>C) is classified Uncertain significance in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). AlphaMissense: likely benign (0.1345); Very rare (popmax 0.00167%, amr); Associated with autosomal dominant polycystic kidney disease.

What condition is associated with PKD2 p.Ser795Pro (c.2383T>C)?

PKD2 p.Ser795Pro (c.2383T>C) is associated with autosomal dominant polycystic kidney disease (ClinVar).

How common is PKD2 p.Ser795Pro (c.2383T>C) in the general population?

PKD2 p.Ser795Pro (c.2383T>C) is very rare (popmax 0.00167%, amr) (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.Ser795Pro (c.2383T>C)?

AlphaMissense predicts likely benign (score 0.1345) — an in-silico prediction, not a clinical call.

PKD2 p.Ser795Pro

c.2383T>C · rs1203706764 · VCV1924576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1345 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal dominant polycystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.1345	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	25.3	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 0.00167% Admixed American · 1/60,006 alleles

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 1/1,461,760 · genomes 0/152,252 · joint denominator

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.Ser795Pro
Coding: c.2383T>C
MANE Select: NM_000297
dbSNP: rs1203706764
Type: single nucleotide variant
Location: chr4:88067922 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 795: the protein kinase 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

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.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
PKD2 c.2522+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-ser795pro (accessed [today's date]).

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