Is CYBA p.Thr191fs (c.571_*16del) pathogenic?

CYBA p.Thr191fs (c.57116del) is classified Likely pathogenic in CYBA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). Associated with chronic granulomatous disease.

What condition is associated with CYBA p.Thr191fs (c.571_*16del)?

CYBA p.Thr191fs (c.571_*16del) is associated with chronic granulomatous disease (ClinVar).

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.Thr191fs

c.571_*16del · VCV4817431

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

chronic granulomatous disease

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 1.3	GERP 0.24, phastCons 0.014

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

Variant & gene context

Gene: CYBA
Protein: p.Thr191fs
Coding: c.571_*16del
MANE Select: NM_000101
Type: Deletion
Location: chr16:88643337 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 191: the 'disordered' region

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

Disease context

chronic granulomatous disease — 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.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.Lys60fs Likely pathogenic ★ same condition
CYBA p.Tyr41fs Likely pathogenic ★ same condition
CYBA p.Thr191= Likely benign ★ same residue
CYBA p.Arg141_Pro142del Uncertain significance same condition
CYBA c.128+2T>C 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-thr191fs (accessed [today's date]).

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