Is GNB1 p.Arg134= (c.402C>T) pathogenic?

GNB1 p.Arg134= (c.402C>T) is classified Likely benign in GNB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). Ultra-rare (popmax 0.0283%, amr); Associated with myelodysplastic syndrome.

What condition is associated with GNB1 p.Arg134= (c.402C>T)?

GNB1 p.Arg134= (c.402C>T) is associated with myelodysplastic syndrome, acute lymphoblastic leukemia, intellectual disability, autosomal dominant 42 (ClinVar).

How common is GNB1 p.Arg134= (c.402C>T) in the general population?

GNB1 p.Arg134= (c.402C>T) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

GNB1 p.Arg134=

c.402C>T · rs560214051 · VCV1562666

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Conditions

myelodysplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.7	GERP -5.4
Overall
CADD	3.401	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/59,994 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00322% 52/1,613,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,529
South Asian	0.0154%	6,504
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Finnishnot grpmax-eligible	0.00469%	21,339
East Asian	0.00223%	44,878
African / African-American	0.00133%	74,988
European (non-Finnish)	0.000678%	147,460

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.Arg134=
Coding: c.402C>T
MANE Select: NM_002074
dbSNP: rs560214051
Type: single nucleotide variant
Location: chr1:1804447 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 97.04 · 1043 PDB
Residue 134: a β-strand

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

Disease context

myelodysplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute lymphoblastic leukemia intellectual disability, autosomal dominant 42

Similar variants

GNB1 p.Arg134His Uncertain significance ★★ ⚠ same residue
GNB1 c.498-2A>G Likely pathogenic ★★ same condition
GNB1 p.Ala73Ser Pathogenic/Likely pathogenic ★★ same condition
GNB1 p.Ala73Thr Pathogenic/Likely pathogenic ★★ same condition
GNB1 p.Ala92Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
GNB1 p.Asp118Gly Pathogenic ★★ same condition
GNB1 p.Asp118His Likely pathogenic ★★ same condition
GNB1 p.Asp118Tyr 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/gnb1-p-arg134 (accessed [today's date]).

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