Is CYBA p.Lys58fs (c.171del) pathogenic?

CYBA p.Lys58fs (c.171del) is classified Pathogenic in CYBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-17). Absent from gnomAD; Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Lys58fs (c.171del)?

CYBA p.Lys58fs (c.171del) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Lys58fs (c.171del) in the general population?

CYBA p.Lys58fs (c.171del) 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.

CYBA p.Lys58fs

c.171del · rs763678131 · VCV872524

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.61, phastCons 0.06

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: CYBA
Protein: p.Lys58fs
Coding: c.171del
MANE Select: NM_000101
dbSNP: rs763678131
Type: Deletion
Location: chr16:88647133 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB

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.Lys58Arg Uncertain significance ★★ ⚠ same residue
CYBA p.Lys58= Likely benign ★ same residue
CYBA c.288-3_300del Likely pathogenic ★★ same condition
CYBA p.Arg90fs Pathogenic/Likely pathogenic ★★ same condition
CYBA p.Ile26fs Pathogenic/Likely pathogenic ★★ same condition
CYBA p.Val99fs Pathogenic/Likely pathogenic ★★ same condition
CYBA c.203+102_404del Likely pathogenic ★ same condition
CYBA c.58+6_58+15del 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/cyba-p-lys58fs (accessed [today's date]).

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