Is CYBB p.Lys315del (c.937AAG[2]) pathogenic?

CYBB p.Lys315del (c.937AAG[2]) is classified Conflicting classifications of pathogenicity in CYBB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-29). Absent from gnomAD; Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Lys315del (c.937AAG[2])?

CYBB p.Lys315del (c.937AAG[2]) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Lys315del (c.937AAG[2]) in the general population?

CYBB p.Lys315del (c.937AAG[2]) 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.Lys315del

c.937AAG[2] · rs2146817067 · VCV1200057

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

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.Lys315del
Coding: c.937AAG[2]
MANE Select: NM_000397
dbSNP: rs2146817067
Type: Microsatellite
Location: chrX:37803915 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 315: the fad-binding fr-type domain; a UniProt-annotated variant site (in cgdx)

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.Lys315= Likely benign ★ same residue
CYBB c.674+4_674+7del Pathogenic ★★ same condition
CYBB p.His303fs Pathogenic ★ same condition
CYBB p.Phe216del Pathogenic ★ same condition
CYBB p.Ser235fs Pathogenic ★ same condition
CYBB p.Leu458del Uncertain significance ★ same condition
CYBB c.805-10_805-9del Likely benign ★ same condition
CYBB c.1315-2A>G Pathogenic/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-lys315del (accessed [today's date]).

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