Is PKHD1 p.Pro296= (c.888A>T) pathogenic?

PKHD1 p.Pro296= (c.888A>T) is classified Benign/Likely benign in PKHD1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.97%, afr); Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Pro296= (c.888A>T)?

PKHD1 p.Pro296= (c.888A>T) is associated with autosomal recessive polycystic kidney disease, polycystic kidney disease (ClinVar).

How common is PKHD1 p.Pro296= (c.888A>T) in the general population?

PKHD1 p.Pro296= (c.888A>T) is low-frequency (popmax 2.97%, afr) (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.Pro296=

c.888A>T · rs76012218 · VCV220081

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.97%, afr)

Conditions

autosomal recessive polycystic kidney disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.8	GERP -4.4
Overall
CADD	3.993	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.97% African / African-American · 2,108/70,922 alleles

Filtering AF 2.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.82%

Overall 0.162% 2,557/1,581,134 alleles · low-frequency exomes 1,308/1,435,460 · genomes 1,249/145,674 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.97%	34
Middle Eastern	0.27%	370
Remaining individualsnot grpmax-eligible	0.257%	389
Admixed American	0.257%	390
European (non-Finnish)	0.0104%	9,602
South Asian	0.00443%	22,574
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,822

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.Pro296=
Coding: c.888A>T
MANE Select: NM_138694
dbSNP: rs76012218
Type: single nucleotide variant
Location: chr6:52065043 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 296: the ipt/tig 3 domain

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

Also linked: polycystic kidney disease

For Autosomal recessive polycystic kidney disease (Orphanet):

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

Similar variants

PKHD1 c.11174+2T>C Likely pathogenic ★★ same condition
PKHD1 c.11310+1G>C Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.11398+2T>C Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.11507-1G>A Likely pathogenic ★★ same condition
PKHD1 c.11665+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.1233+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.131-1G>A Likely pathogenic ★★ same condition
PKHD1 c.1513-1G>A 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-pro296 (accessed [today's date]).

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