Is CYBA p.Pro157fs (c.467dup) pathogenic?

CYBA p.Pro157fs (c.467dup) is classified Pathogenic/Likely pathogenic in CYBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). Absent from gnomAD v4.1; Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Pro157fs (c.467dup)?

CYBA p.Pro157fs (c.467dup) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Pro157fs (c.467dup) in the general population?

CYBA p.Pro157fs (c.467dup) is absent from gnomAD v4.1 (gnomAD).

How is Chronic granulomatous disease inherited?

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

CYBA p.Pro157fs

c.467dup · rs2507521330 · VCV1977314

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,406)

Conditions

granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9	GERP -2.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,532,406). 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: CYBA
Protein: p.Pro157fs
Coding: c.467dup
MANE Select: NM_000101
dbSNP: rs2507521330
Type: Duplication
Location: chr16:88643473 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 157: the 'disordered' region; an α-helix

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

Disease context

granulomatous disease, chronic, autosomal recessive, cytochrome b-negative — 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

CYBA p.Pro157Leu Uncertain significance ★ ⚠ same residue
CYBA p.Pro157= Likely benign ★ same residue
CYBA p.Arg56fs Pathogenic ★★ same condition
CYBA c.204-9_204-3dup Likely benign ★★ same condition
CYBA p.Tyr37fs Pathogenic ★ same condition
CYBA p.Glu129_Ile144dup Uncertain significance ★ same condition
CYBA p.Gly182fs Uncertain significance ★ same condition
CYBA c.58+10dup Likely benign ★ 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/cyba-p-pro157fs (accessed [today's date]).

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