Is PKHD1 p.Pro682fs (c.2045del) pathogenic?

PKHD1 p.Pro682fs (c.2045del) is classified Likely pathogenic in PKHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Very rare (popmax 6.84e-05%); Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Pro682fs (c.2045del)?

PKHD1 p.Pro682fs (c.2045del) is associated with autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Pro682fs (c.2045del) in the general population?

PKHD1 p.Pro682fs (c.2045del) is very rare (popmax 6.84e-05%) (gnomAD).

How is Autosomal recessive polycystic kidney disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PKHD1 p.Pro682fs

c.2045del · VCV4816597

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

autosomal recessive polycystic kidney disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 67
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -4.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,850 alleles · very rare

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: PKHD1
Protein: p.Pro682fs
Coding: c.2045del
MANE Select: NM_138694
Type: Deletion
Location: chr6:52053171 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 682: a UniProt-annotated variant site (found in a patient affected by polycystic liver disease; uncertain significance)

Full PKHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive polycystic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive polycystic kidney disease (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

PKHD1 p.Pro682= Likely benign ★ same residue
PKHD1 c.131delG Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.3229-2del Likely pathogenic ★★ same condition
PKHD1 c.5909-2del Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.5909-46_5943del Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.6866-16_6866del Likely pathogenic ★★ same condition
PKHD1 p.Ala1826fs Pathogenic/Likely pathogenic ★★ same condition
PKHD1 p.Ala2031fs 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/pkhd1-p-pro682fs (accessed [today's date]).

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