Is PKD2 p.Leu796Ser (c.2387T>C) pathogenic?

PKD2 p.Leu796Ser (c.2387T>C) is classified Uncertain significance in PKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-21). AlphaMissense: likely benign (0.2838); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PKD2 p.Leu796Ser (c.2387T>C)?

PKD2 p.Leu796Ser (c.2387T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PKD2 p.Leu796Ser (c.2387T>C) in the general population?

PKD2 p.Leu796Ser (c.2387T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PKD2 p.Leu796Ser (c.2387T>C)?

AlphaMissense predicts likely benign (score 0.2838) — an in-silico prediction, not a clinical call.

PKD2 p.Leu796Ser

c.2387T>C · VCV4861976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2838	likely benign
REVEL	0.509	indeterminate
SaProt	LLR -5.59	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 4.9	GERP 1.8, phastCons 0.91
Overall
CADD	24.8	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

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.Leu796Ser
Coding: c.2387T>C
MANE Select: NM_000297
Type: single nucleotide variant
Location: chr4:88067926 (GRCh38)
Structure: AlphaFold pLDDT 69.85 · 4 PDB
Residue 796: the protein kinase domain

Full PKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PKD2 p.Leu796Ter Likely pathogenic ★ same residue
PKD2 p.Leu796= Conflicting classifications of pathogenicity ★ same residue
PKD2 p.Leu796Phe Uncertain significance ★ ⚠ same residue
PKD2 p.Arg654Ter Pathogenic/Likely pathogenic ★★ same condition
PKD2 p.Gly363Ter Pathogenic ★★ same condition
PKD2 p.Tyr836Ter Pathogenic ★★ same condition
PKD2 p.Ala303Gly Uncertain significance ★★ ⚠ same condition
PKD2 p.Ala407Thr Uncertain significance ★★ ⚠ 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-leu796ser (accessed [today's date]).

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