Is PKHD1 p.Asp43= (c.129T>C) pathogenic?

PKHD1 p.Asp43= (c.129T>C) is classified Conflicting classifications of pathogenicity in PKHD1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-08-04). Ultra-rare (popmax 0.0617%, amr); Associated with polycystic kidney disease 4.

What condition is associated with PKHD1 p.Asp43= (c.129T>C)?

PKHD1 p.Asp43= (c.129T>C) is associated with polycystic kidney disease 4, autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Asp43= (c.129T>C) in the general population?

PKHD1 p.Asp43= (c.129T>C) is ultra-rare (popmax 0.0617%, amr) (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.Asp43=

c.129T>C · rs201195801 · VCV281794

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

Conditions

polycystic kidney disease 4

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 0.47	GERP 1.5, phastCons 0.73
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0617% Admixed American · 37/59,998 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.0306% 489/1,599,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,622
European (non-Finnish)	0.0358%	2,790
Remaining individualsnot grpmax-eligible	0.029%	3,445
Middle Eastern	0.0165%	6,044
Finnishnot grpmax-eligible	0.0156%	6,401
African / African-American	0.00536%	18,652
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,494

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.Asp43=
Coding: c.129T>C
MANE Select: NM_138694
dbSNP: rs201195801
Type: single nucleotide variant
Location: chr6:52083179 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 43: the ipt/tig 1; atypical 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.Asp43Gly Uncertain significance ★ ⚠ same residue
PKHD1 p.Asp43Val 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
PKHD1 c.11666-2A>G 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-asp43 (accessed [today's date]).

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