Is PKHD1 p.Val96= (c.288G>A) pathogenic?

PKHD1 p.Val96= (c.288G>A) is classified Likely benign in PKHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-20). Ultra-rare (popmax 0.0177%, sas); Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Val96= (c.288G>A)?

PKHD1 p.Val96= (c.288G>A) is associated with autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Val96= (c.288G>A) in the general population?

PKHD1 p.Val96= (c.288G>A) is ultra-rare (popmax 0.0177%, sas) (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.Val96=

c.288G>A · rs755771472 · VCV1133050

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, sas)

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 0.42	GERP 1.7, phastCons 0.39
Overall
CADD	6.343	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0177% South Asian · 16/90,554 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00119% 17/1,434,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0177%	5,660
Remaining individualsnot grpmax-eligible	0.00163%	61,496

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.Val96=
Coding: c.288G>A
MANE Select: NM_138694
dbSNP: rs755771472
Type: single nucleotide variant
Location: chr6:52080002 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 96: the ipt/tig 1; atypical 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

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-val96 (accessed [today's date]).

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