Is CYBB p.Glu555Ter (c.1662dup) pathogenic?

CYBB p.Glu555Ter (c.1662dup) is classified Pathogenic/Likely pathogenic in CYBB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Very rare (popmax 9.14e-05%); Associated with X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency.

How common is CYBB p.Glu555Ter (c.1662dup) in the general population?

CYBB p.Glu555Ter (c.1662dup) is very rare (popmax 9.14e-05%) (gnomAD).

CYBB p.Glu555Ter

Q: What condition is associated with CYBB p.Glu555Ter (c.1662dup)?

CYBB p.Glu555Ter (c.1662dup) is associated with X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency, granulomatous disease, chronic, X-linked (ClinVar).

Q: How is X-linked mendelian susceptibility to mycobacterial diseases inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1662dup · rs1453468510 · VCV418153

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.14e-05%)

Conditions

X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.14e-05%

Overall 9.14e-05% 1/1,093,950 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CYBB
Protein: p.Glu555Ter
Coding: c.1662dup
MANE Select: NM_000397
dbSNP: rs1453468510
Type: Duplication
Location: chrX:37810865 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB

Full CYBB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: granulomatous disease, chronic, X-linked

For X-linked mendelian susceptibility to mycobacterial diseases (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

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
CYBB p.Ile439fs Pathogenic ★ same condition
CYBB p.Leu173fs 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-glu555ter (accessed [today's date]).

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