Is PKHD1 p.Arg1997= (c.5989C>A) pathogenic?

PKHD1 p.Arg1997= (c.5989C>A) is classified Likely benign in PKHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.016%, afr); Associated with polycystic kidney disease 4.

What condition is associated with PKHD1 p.Arg1997= (c.5989C>A)?

PKHD1 p.Arg1997= (c.5989C>A) is associated with polycystic kidney disease 4, autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Arg1997= (c.5989C>A) in the general population?

PKHD1 p.Arg1997= (c.5989C>A) is ultra-rare (popmax 0.016%, 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.Arg1997=

c.5989C>A · rs369801937 · VCV1078879

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

polycystic kidney disease 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP -0.17, phastCons 1
Overall
CADD	9.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,906 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000806% 13/1,613,708 alleles · ultra-rare exomes 3/1,461,554 · genomes 10/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
Admixed American	0.00167%	60,000

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.Arg1997=
Coding: c.5989C>A
MANE Select: NM_138694
dbSNP: rs369801937
Type: single nucleotide variant
Location: chr6:51934242 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 1997: a UniProt-annotated variant site (found in a patient affected by polycystic liver disease; uncertain significance); the g8 1 domain

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

Disease context

polycystic kidney disease 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive 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 p.Arg1997Trp Uncertain significance ★ same residue
PKHD1 p.Arg1997Gly Uncertain significance same residue
PKHD1 p.Arg1997Gln Uncertain significance ★ ⚠ same residue
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

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-arg1997 (accessed [today's date]).

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