Is CYBB p.Asn489fs (c.1465_1466insC) pathogenic?

CYBB p.Asn489fs (c.14651466insC) is classified Likely pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Asn489fs (c.1465_1466insC)?

CYBB p.Asn489fs (c.1465_1466insC) 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.Asn489fs

c.1465_1466insC · VCV4071545

Likely pathogenic Single submitter

Classification

Likely 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 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.55, phastCons 0.3

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

Variant & gene context

Gene: CYBB
Protein: p.Asn489fs
Coding: c.1465_1466insC
MANE Select: NM_000397
Type: Insertion
Location: chrX:37809570 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 489: 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.Asn489Ser Uncertain significance ★ ⚠ same residue
CYBB c.1151+9_1151+10insTA Likely benign ★ same condition
CYBB c.484-14_484-13insAT Likely benign ★ same condition
CYBB c.484-262_484-261insLINE1 Pathogenic same condition
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

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-asn489fs (accessed [today's date]).

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