Is CYBB p.Val14fs (c.40del) pathogenic?

CYBB p.Val14fs (c.40del) is classified Pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-18). Absent from gnomAD; Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Val14fs (c.40del)?

CYBB p.Val14fs (c.40del) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Val14fs (c.40del) in the general population?

CYBB p.Val14fs (c.40del) is absent from gnomAD (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.Val14fs

c.40del · rs2519189260 · VCV2138518

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CYBB
Protein: p.Val14fs
Coding: c.40del
MANE Select: NM_000397
dbSNP: rs2519189260
Type: Deletion
Location: chrX:37780117 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 14: 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.Val14= Likely benign ★ same residue
CYBB p.Glu347fs Pathogenic ★★ same condition
CYBB p.Glu540fs Likely pathogenic ★★ same condition
CYBB p.Val27fs Pathogenic ★★ same condition
CYBB p.Val321fs Pathogenic ★★ same condition
CYBB c.1150_1151+2del Pathogenic ★ same condition
CYBB c.141+1del Pathogenic ★ same condition
CYBB c.37_45+2del 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-val14fs (accessed [today's date]).

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