Is CYBA p.Ile144= (c.432C>T) pathogenic?

CYBA p.Ile144= (c.432C>T) is classified Likely benign in CYBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). Ultra-rare (popmax 0.011%, afr); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Ile144= (c.432C>T)?

CYBA p.Ile144= (c.432C>T) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Ile144= (c.432C>T) in the general population?

CYBA p.Ile144= (c.432C>T) is ultra-rare (popmax 0.011%, afr) (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.Ile144=

c.432C>T · rs760991073 · VCV1096333

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, afr)

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 -5.1	GERP -3.2
Overall
CADD	3.148	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% African / African-American · 8/72,838 alleles

Filtering AF 0.00541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.00313% 48/1,534,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.011%	9,105
South Asian	0.00357%	27,977
European (non-Finnish)	0.00305%	32,751
Admixed American	0.00196%	50,944
Remaining individualsnot grpmax-eligible	0.00167%	59,724

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.Ile144=
Coding: c.432C>T
MANE Select: NM_000101
dbSNP: rs760991073
Type: single nucleotide variant
Location: chr16:88643509 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 144: the 'disordered' region

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 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
CYBA p.Ala124Val 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-ile144 (accessed [today's date]).

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