Is CYBB p.Ile439fs (c.1313dup) pathogenic?

CYBB p.Ile439fs (c.1313dup) is classified Pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-26). Ultra-rare (gnomAD MAF 9.516e-07); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Ile439fs (c.1313dup)?

CYBB p.Ile439fs (c.1313dup) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Ile439fs (c.1313dup) in the general population?

CYBB p.Ile439fs (c.1313dup) is ultra-rare (gnomAD MAF 9.516e-07) (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.Ile439fs

c.1313dup · rs1602183698 · VCV646067

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 9.516e-07)

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 10 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.005	GERP -2.2, phastCons 0.61

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

Population frequency

dbSNP / gnomAD

Global frequency 9.52e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CYBB
Protein: p.Ile439fs
Coding: c.1313dup
MANE Select: NM_000397
dbSNP: rs1602183698
Type: Duplication
Location: chrX:37805162 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 439: a β-strand

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.Ile439= Likely benign ★ 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-ile439fs (accessed [today's date]).

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