Is GANAB p.Pro59fs (c.174_175del) pathogenic?

GANAB p.Pro59fs (c.174175del) is classified Likely pathogenic in GANAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). Very rare (popmax 8.48e-05%, nfe); Associated with polycystic kidney disease 3 with or without polycystic liver disease.

What condition is associated with GANAB p.Pro59fs (c.174_175del)?

GANAB p.Pro59fs (c.174_175del) is associated with polycystic kidney disease 3 with or without polycystic liver disease (ClinVar).

How common is GANAB p.Pro59fs (c.174_175del) in the general population?

GANAB p.Pro59fs (c.174_175del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

GANAB p.Pro59fs

c.174_175del · rs2539030948 · VCV3236803

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

polycystic kidney disease 3 with or without polycystic liver disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 4.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,776 alleles

Overall 6.2e-05% 1/1,613,792 alleles · very rare exomes 1/1,461,624 · genomes 0/152,168 · joint denominator

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: GANAB
Protein: p.Pro59fs
Coding: c.174_175del
MANE Select: NM_198334
dbSNP: rs2539030948
Type: Microsatellite
Location: chr11:62639436 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB
Residue 59: a β-strand

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

Disease context

polycystic kidney disease 3 with or without polycystic liver disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

GANAB p.Arg51fs Pathogenic/Likely pathogenic ★★ same condition
GANAB p.Leu67fs Pathogenic/Likely pathogenic ★★ same condition
GANAB c.1738-15TC[2] Uncertain significance ★ same condition
GANAB p.Phe652del Uncertain significance ★ same condition
GANAB p.Arg112Ter Likely pathogenic ★★ same condition
GANAB p.Arg164Ter Pathogenic/Likely pathogenic ★★ same condition
GANAB p.Arg812Ter Pathogenic/Likely pathogenic ★★ same condition
GANAB p.Arg815Ter 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/ganab-p-pro59fs (accessed [today's date]).

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