Is CYBA p.Lys60= (c.180G>A) pathogenic?

CYBA p.Lys60= (c.180G>A) is classified Likely benign in CYBA (ClinVar, Single submitter, 2 submitters; last evaluated 2022-06-13). Very rare (popmax 8.48e-05%, nfe); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

How common is CYBA p.Lys60= (c.180G>A) in the general population?

CYBA p.Lys60= (c.180G>A) is very rare (popmax 8.48e-05%, nfe) (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.Lys60=

Q: What condition is associated with CYBA p.Lys60= (c.180G>A)?

CYBA p.Lys60= (c.180G>A) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative, chronic granulomatous disease (ClinVar).

c.180G>A · rs1597372473 · VCV2005967

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -2.8
Overall
CADD	3.239	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,810 alleles

Overall 6.21e-05% 1/1,611,522 alleles · very rare exomes 1/1,459,188 · genomes 0/152,334 · joint denominator

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: CYBA
Protein: p.Lys60=
Coding: c.180G>A
MANE Select: NM_000101
dbSNP: rs1597372473
Type: single nucleotide variant
Location: chr16:88647124 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 60: a β-strand

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

Also linked: chronic granulomatous disease

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.Lys60Thr Benign/Likely benign ★★ same residue
CYBA p.Lys60Arg Uncertain significance ★ ⚠ same residue
CYBA p.Lys60fs Likely pathogenic ★ same residue
CYBA p.Lys60Met Uncertain significance ★ ⚠ same residue
CYBA c.128+2T>C Likely pathogenic ★★ same condition
CYBA c.204-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYBA c.287+1G>T Pathogenic/Likely pathogenic ★★ same condition
CYBA c.287+2T>C 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/cyba-p-lys60 (accessed [today's date]).

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