Is GANAB p.Val648= (c.1944G>A) pathogenic?

GANAB p.Val648= (c.1944G>A) is classified Uncertain significance in GANAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). Very rare (popmax 0.00763%, nfe); Associated with polycystic kidney disease 3 with or without polycystic liver disease.

What condition is associated with GANAB p.Val648= (c.1944G>A)?

GANAB p.Val648= (c.1944G>A) is associated with polycystic kidney disease 3 with or without polycystic liver disease (ClinVar).

How common is GANAB p.Val648= (c.1944G>A) in the general population?

GANAB p.Val648= (c.1944G>A) is very rare (popmax 0.00763%, 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.Val648=

c.1944G>A · VCV3599853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00763%, 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP 3, phastCons 1
Overall
CADD	15.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00763% European (non-Finnish) · 90/1,178,790 alleles

Filtering AF 0.00632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00585%

Overall 0.00583% 94/1,612,578 alleles · very rare exomes 93/1,460,428 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,098
Remaining individualsnot grpmax-eligible	0.00481%	20,806
African / African-American	0.00134%	74,878

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.Val648=
Coding: c.1944G>A
MANE Select: NM_198334
Type: single nucleotide variant
Location: chr11:62629005 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB

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.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
GANAB c.560+451C>T Uncertain significance ★★ 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-val648 (accessed [today's date]).

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