Is CYBB p.Thr183= (c.549G>A) pathogenic?

CYBB p.Thr183= (c.549G>A) is classified Benign in CYBB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-15). Ultra-rare (popmax 0.0159%, sas); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Thr183= (c.549G>A)?

CYBB p.Thr183= (c.549G>A) is associated with granulomatous disease, chronic, X-linked, chronic granulomatous disease (ClinVar).

How common is CYBB p.Thr183= (c.549G>A) in the general population?

CYBB p.Thr183= (c.549G>A) is ultra-rare (popmax 0.0159%, sas) (gnomAD).

How is Chronic granulomatous disease inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CYBB p.Thr183=

c.549G>A · rs1556468340 · VCV1169993

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, sas)

Conditions

granulomatous disease, chronic, X-linked

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 -0.37	GERP -3.5
Overall
CADD	0.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% South Asian · 9/56,605 alleles

Filtering AF 0.00825% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00619%

Overall 0.00117% 14/1,201,258 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0159%	6,289
European (non-Finnish)	0.000562%	177,946

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: CYBB
Protein: p.Thr183=
Coding: c.549G>A
MANE Select: NM_000397
dbSNP: rs1556468340
Type: single nucleotide variant
Location: chrX:37796016 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 183: an α-helix; the ferric oxidoreductase domain

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

Disease context

granulomatous disease, chronic, X-linked — 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

CYBB p.Thr183Met Uncertain significance ★ ⚠ same residue
CYBB c.1151+2T>C Pathogenic ★★ same condition
CYBB c.1315-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYBB c.141+1G>T Pathogenic ★★ same condition
CYBB c.252+5G>A Pathogenic ★★ same condition
CYBB c.483+1G>A Pathogenic ★★ same condition
CYBB c.483+1G>T Pathogenic ★★ same condition
CYBB c.483+3A>T 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/cybb-p-thr183 (accessed [today's date]).

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