Is PKHD1 p.Pro2072= (c.6216T>G) pathogenic?

PKHD1 p.Pro2072= (c.6216T>G) is classified Conflicting classifications of pathogenicity in PKHD1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0907%, afr); Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Pro2072= (c.6216T>G)?

PKHD1 p.Pro2072= (c.6216T>G) is associated with autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Pro2072= (c.6216T>G) in the general population?

PKHD1 p.Pro2072= (c.6216T>G) is ultra-rare (popmax 0.0907%, 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.Pro2072=

c.6216T>G · rs148817026 · VCV197050

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0907%, 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 -0.057	GERP -5.7, phastCons 0.022
Overall
CADD	4.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0907% African / African-American · 68/74,984 alleles

Filtering AF 0.0733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0671%

Overall 0.00552% 89/1,612,700 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0907%	1,103
Admixed American	0.0167%	5,994
Remaining individualsnot grpmax-eligible	0.0032%	31,218
European (non-Finnish)	0.000763%	130,983

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.Pro2072=
Coding: c.6216T>G
MANE Select: NM_138694
dbSNP: rs148817026
Type: single nucleotide variant
Location: chr6:51912482 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 2072: a UniProt-annotated variant site (found in a patient affected by polycystic liver disease; uncertain significance)

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-pro2072 (accessed [today's date]).

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