Is PKD1 p.Leu3526Val (c.10576C>G) pathogenic?

PKD1 p.Leu3526Val (c.10576C>G) is classified Uncertain significance in PKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely benign (0.0833); Absent from gnomAD v4.1; Associated with polycystic kidney disease 1.

What condition is associated with PKD1 p.Leu3526Val (c.10576C>G)?

PKD1 p.Leu3526Val (c.10576C>G) is associated with polycystic kidney disease 1 (ClinVar).

How common is PKD1 p.Leu3526Val (c.10576C>G) in the general population?

PKD1 p.Leu3526Val (c.10576C>G) 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 PKD1 p.Leu3526Val (c.10576C>G)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

PKD1 p.Leu3526Val

c.10576C>G · VCV3579009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.34, phastCons 0.084
Regional constraint	o/e 1.29	unconstrained · MANE · 11 kb · p 1.9e-30 · regional, not allelic
Overall
CADD	5.817	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 is an independent agreement signal.

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: PKD1
Protein: p.Leu3526Val
Coding: c.10576C>G
MANE Select: NM_001009944
Type: single nucleotide variant
Location: chr16:2094134 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full PKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 1 — 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

PKD1 p.Leu3526= Likely benign ★★ same residue
PKD1 c.10619-2A>G Pathogenic ★★ same condition
PKD1 c.10821+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.10821+2T>G Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-10C>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-25A>C Likely pathogenic ★★ same condition
PKD1 c.11017-25A>G Likely pathogenic ★★ same condition
PKD1 c.11269+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/pkd1-p-leu3526val (accessed [today's date]).

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