Is PKHD1 p.Pro1255fs (c.3762_3763insG) pathogenic?

PKHD1 p.Pro1255fs (c.37623763insG) is classified Likely pathogenic in PKHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-14). Absent from gnomAD; Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Pro1255fs (c.3762_3763insG)?

PKHD1 p.Pro1255fs (c.3762_3763insG) is associated with autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Pro1255fs (c.3762_3763insG) in the general population?

PKHD1 p.Pro1255fs (c.3762_3763insG) is absent from gnomAD (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.Pro1255fs

c.3762_3763insG · rs1802132538 · VCV981065

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 32 of 67
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP -2.5

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PKHD1
Protein: p.Pro1255fs
Coding: c.3762_3763insG
MANE Select: NM_138694
dbSNP: rs1802132538
Type: Insertion
Location: chr6:52026047 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 1255: the ipt/tig 7 domain; 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.Pro1255= Likely benign ★ same residue
PKHD1 p.Asp2689fs Likely pathogenic ★ same condition
PKHD1 p.Cys3405fs Likely pathogenic ★ same condition
PKHD1 p.Gln367fs Likely pathogenic ★ same condition
PKHD1 p.Glu2823fs Likely pathogenic ★ same condition
PKHD1 p.Glu696fs Pathogenic ★ same condition
PKHD1 p.Gly378fs Pathogenic ★ same condition
PKHD1 p.Ile794fs 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-pro1255fs (accessed [today's date]).

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