Is GNB3 p.Val39fs (c.116del) pathogenic?

GNB3 p.Val39fs (c.116del) is classified Likely pathogenic in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-21). Associated with GNB3-related disorders.

What condition is associated with GNB3 p.Val39fs (c.116del)?

GNB3 p.Val39fs (c.116del) is associated with GNB3-related disorders (ClinVar).

GNB3 p.Val39fs

c.116del · VCV4915438

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

GNB3-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -1.3, phastCons 1

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

Variant & gene context

Gene: GNB3
Protein: p.Val39fs
Coding: c.116del
MANE Select: NM_002075
Type: Deletion
Location: chr12:6842989 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 2 PDB

Full GNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GNB3-related disorders

Similar variants

GNB3 p.Glu38fs Likely pathogenic ★ same condition
GNB3 p.Asn237fs Conflicting classifications of pathogenicity ★ same condition
GNB3 c.57+2T>C Likely pathogenic ★ same condition
GNB3 p.Cys121Ter Likely pathogenic ★ same condition
GNB3 c.430+1G>A Conflicting classifications of pathogenicity ★ same condition
GNB3 c.96+2T>G Conflicting classifications of pathogenicity ★ same condition
GNB3 p.Trp211Ter Conflicting classifications of pathogenicity ★ same condition
GNB3 c.699+115del Benign/Likely benign ★★ same type

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/gnb3-p-val39fs (accessed [today's date]).

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