Is GNB4 p.Arg68= (c.204G>A) pathogenic?

GNB4 p.Arg68= (c.204G>A) is classified Likely benign in GNB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). Ultra-rare (popmax 0.0114%, eas); Associated with Inborn genetic diseases.

What condition is associated with GNB4 p.Arg68= (c.204G>A)?

GNB4 p.Arg68= (c.204G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GNB4 p.Arg68= (c.204G>A) in the general population?

GNB4 p.Arg68= (c.204G>A) is ultra-rare (popmax 0.0114%, eas) (gnomAD).

GNB4 p.Arg68=

c.204G>A · VCV3520944

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Overall
CADD	19.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% East Asian · 5/43,858 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00291%

Overall 0.000378% 6/1,585,616 alleles · ultra-rare exomes 5/1,433,594 · genomes 1/152,022 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0114%	8,772
Admixed American	0.00181%	55,130

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: GNB4
Protein: p.Arg68=
Coding: c.204G>A
MANE Select: NM_021629
Type: single nucleotide variant
Location: chr3:179416556 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 97.14

Full GNB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNB4 p.Arg137Ter Uncertain significance ★★ same condition
GNB4 p.Arg214Ter Uncertain significance ★★ same condition
GNB4 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
GNB4 p.Arg251Gln Uncertain significance ★★ ⚠ same condition
GNB4 p.Arg304Cys Uncertain significance ★★ ⚠ same condition
GNB4 p.Arg314His Uncertain significance ★★ ⚠ same condition
GNB4 p.Asp303Ala Uncertain significance ★★ ⚠ same condition
GNB4 p.Gly288Ala 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/gnb4-p-arg68 (accessed [today's date]).

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