Is CYBA p.Phe80= (c.240C>T) pathogenic?

CYBA p.Phe80= (c.240C>T) is classified Likely benign in CYBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.0209%, nfe); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Phe80= (c.240C>T)?

CYBA p.Phe80= (c.240C>T) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Phe80= (c.240C>T) in the general population?

CYBA p.Phe80= (c.240C>T) is ultra-rare (popmax 0.0209%, 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.Phe80=

c.240C>T · rs373948664 · VCV466300

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, 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 -8.7	GERP -2.9
Overall
CADD	3.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% European (non-Finnish) · 247/1,179,970 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.016% 258/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0209%	4,777
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Finnishnot grpmax-eligible	0.00156%	63,912

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.Phe80=
Coding: c.240C>T
MANE Select: NM_000101
dbSNP: rs373948664
Type: single nucleotide variant
Location: chr16:88646802 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 80: 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.Phe80Leu 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
CYBA c.288-1G>T Pathogenic/Likely pathogenic ★★ same condition
CYBA c.369+1G>A Likely pathogenic ★★ same condition
CYBA c.58+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-phe80 (accessed [today's date]).

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