Is GNB1 p.Ter341= (c.1022A>G) pathogenic?

GNB1 p.Ter341= (c.1022A>G) is classified Likely benign in GNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). Very rare (popmax 0.00724%, nfe).

How common is GNB1 p.Ter341= (c.1022A>G) in the general population?

GNB1 p.Ter341= (c.1022A>G) is very rare (popmax 0.00724%, nfe) (gnomAD).

GNB1 p.Ter341=

c.1022A>G · rs747120803 · VCV1644422

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00724%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Overall
CADD	12.71	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00724% European (non-Finnish) · 83/1,145,926 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00533% 84/1,576,114 alleles · very rare exomes 82/1,423,928 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00724%	13,806
Remaining individualsnot grpmax-eligible	0.00163%	61,166

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: GNB1
Protein: p.Ter341=
Coding: c.1022A>G
MANE Select: NM_002074
dbSNP: rs747120803
Type: single nucleotide variant
Location: chr1:1787332 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 97.04 · 1043 PDB

Full GNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GNB1 p.Ter341Lys Uncertain significance ★ same residue
GNB1 p.Ter341Ser Uncertain significance ★ same residue
GNB1 c.498-2A>G Likely pathogenic ★★ same type
GNB1 p.Ala73Ser Pathogenic/Likely pathogenic ★★ same type
GNB1 p.Ala73Thr Pathogenic/Likely pathogenic ★★ same type
GNB1 p.Ala92Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
GNB1 p.Asp118Gly Pathogenic ★★ same type
GNB1 p.Asp118His Likely pathogenic ★★ 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/gnb1-p-ter341 (accessed [today's date]).

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