Is CYBB p.Phe40fs (c.113_119dup) pathogenic?

CYBB p.Phe40fs (c.113119dup) is classified Pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-02). Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Phe40fs (c.113_119dup)?

CYBB p.Phe40fs (c.113_119dup) is associated with granulomatous disease, chronic, X-linked (ClinVar).

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.Phe40fs

c.113_119dup · VCV3646865

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.73	GERP -0.89

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

Variant & gene context

Gene: CYBB
Protein: p.Phe40fs
Coding: c.113_119dup
MANE Select: NM_000397
Type: Duplication
Location: chrX:37782154 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 40: an α-helix

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.Phe40Ile Uncertain significance ★ ⚠ same residue
CYBB p.Glu555Ter Pathogenic/Likely pathogenic ★★ same condition
CYBB p.Ile248fs Pathogenic ★★ same condition
CYBB p.Lys381fs Pathogenic/Likely pathogenic ★★ same condition
CYBB p.Val413fs Pathogenic/Likely pathogenic ★★ same condition
CYBB c.45+2dup Pathogenic ★ same condition
CYBB p.Gly176fs Pathogenic ★ same condition
CYBB p.Ile187fs 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-phe40fs (accessed [today's date]).

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