Is PKHD1 p.Pro149fs (c.444_445del) pathogenic?

PKHD1 p.Pro149fs (c.444445del) is classified Pathogenic in PKHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-15). Absent from gnomAD; Associated with Enlarged kidney.

What condition is associated with PKHD1 p.Pro149fs (c.444_445del)?

PKHD1 p.Pro149fs (c.444_445del) is associated with Enlarged kidney (ClinVar).

How common is PKHD1 p.Pro149fs (c.444_445del) in the general population?

PKHD1 p.Pro149fs (c.444_445del) is absent from gnomAD (gnomAD).

PKHD1 p.Pro149fs

c.444_445del · rs2128236766 · VCV1328416

Pathogenic Single submitter

Classification

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

Enlarged kidney

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 6 of 67
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

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.Pro149fs
Coding: c.444_445del
MANE Select: NM_138694
dbSNP: rs2128236766
Type: Deletion
Location: chr6:52076279 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 149: the ipt/tig 2 domain

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

Disease context

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

Similar variants

PKHD1 p.Asp3808fs Pathogenic ★ same condition
PKHD1 p.Pro149= Uncertain significance ★ same residue
PKHD1 p.Pro149Leu Uncertain significance ★ same residue
PKHD1 p.Pro149Ser Uncertain significance ★ same residue
PKHD1 p.Val3430fs Pathogenic ★ same condition
PKHD1 c.131delG Pathogenic/Likely pathogenic ★★ same type
PKHD1 c.3229-2del Likely pathogenic ★★ same type
PKHD1 c.5909-2del Pathogenic/Likely pathogenic ★★ same type

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-pro149fs (accessed [today's date]).

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