Is GANAB p.Pro238= (c.714G>A) pathogenic?

GANAB p.Pro238= (c.714G>A) is classified Benign/Likely benign in GANAB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.74%, afr); Associated with polycystic kidney disease 3 with or without polycystic liver disease.

What condition is associated with GANAB p.Pro238= (c.714G>A)?

GANAB p.Pro238= (c.714G>A) is associated with polycystic kidney disease 3 with or without polycystic liver disease (ClinVar).

How common is GANAB p.Pro238= (c.714G>A) in the general population?

GANAB p.Pro238= (c.714G>A) is low-frequency (popmax 4.74%, afr) (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.Pro238=

c.714G>A · rs139305180 · VCV780995

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.74%, afr)

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.48	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -5.2	GERP -9.9
Overall
CADD	1.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.74% African / African-American · 3,557/74,994 alleles

Filtering AF 4.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.56%

Overall 0.247% 3,981/1,613,402 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.74%	21
Remaining individualsnot grpmax-eligible	0.283%	353
Admixed American	0.263%	380
Middle Eastern	0.165%	606
Finnishnot grpmax-eligible	0.0234%	4,269
South Asian	0.00988%	10,119
European (non-Finnish)	0.00466%	21,443

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.Pro238=
Coding: c.714G>A
MANE Select: NM_198334
dbSNP: rs139305180
Type: single nucleotide variant
Location: chr11:62633188 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB
Residue 238: the 'disordered' region

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.Pro238Leu Uncertain significance ★ ⚠ same residue
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
GANAB p.Arg817Trp Likely pathogenic ★★ same condition
GANAB p.Gln414Ter Pathogenic/Likely pathogenic ★★ same condition
GANAB p.Gln837Ter 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-pro238 (accessed [today's date]).

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