Is CYBB p.Arg130Ter (c.388C>T) pathogenic?

CYBB p.Arg130Ter (c.388C>T) is classified Pathogenic in CYBB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-22). Very rare (popmax 0.000112%, nfe); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Arg130Ter (c.388C>T)?

CYBB p.Arg130Ter (c.388C>T) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Arg130Ter (c.388C>T) in the general population?

CYBB p.Arg130Ter (c.388C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

How is Chronic granulomatous disease inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CYBB p.Arg130Ter

c.388C>T · rs180899069 · VCV862779

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Pangolin	Δ0.31	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.6	GERP 0.76, phastCons 1
Overall
CADD	34.0	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 0.000112% European (non-Finnish) · 1/891,810 alleles

Overall 9.14e-05% 1/1,093,875 alleles · very rare

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: CYBB
Protein: p.Arg130Ter
Coding: c.388C>T
MANE Select: NM_000397
dbSNP: rs180899069
Type: single nucleotide variant
Location: chrX:37793715 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 130: an α-helix; the ferric oxidoreductase domain

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

Disease context

granulomatous disease, chronic, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Chronic granulomatous disease (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CYBB p.Arg130Pro Pathogenic ★★ same residue
CYBB p.Arg130= Likely benign ★★ same residue
CYBB c.1315-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYBB c.141+1G>T Pathogenic ★★ same condition
CYBB c.252+5G>A Pathogenic ★★ same condition
CYBB c.483+1G>A Pathogenic ★★ same condition
CYBB c.483+1G>T Pathogenic ★★ same condition
CYBB c.483+3A>T Likely 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/cybb-p-arg130ter (accessed [today's date]).

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