Is CYBB p.Lys334= (c.1002G>A) pathogenic?

CYBB p.Lys334= (c.1002G>A) is classified Benign in CYBB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 17.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Lys334= (c.1002G>A)?

CYBB p.Lys334= (c.1002G>A) is associated with granulomatous disease, chronic, X-linked, 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.

CYBB p.Lys334=

Q: How common is CYBB p.Lys334= (c.1002G>A) in the general population?

CYBB p.Lys334= (c.1002G>A) is common (popmax 17.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1002G>A · rs2228117 · VCV464971

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 17.6%, afr) — too common for a highly-penetrant pathogenic allele

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 0.73	GERP -0.84, phastCons 0.3
Overall
CADD	4.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.6% African / African-American · 10,020/56,935 alleles

Filtering AF 17.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.2%

Overall 0.969% 11,724/1,209,331 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	17.6%	6
Admixed American	1.62%	62
Remaining individualsnot grpmax-eligible	1.44%	69
Middle Eastern	0.391%	256
South Asian	0.0458%	2,184
European (non-Finnish)	0.0261%	3,825

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.Lys334=
Coding: c.1002G>A
MANE Select: NM_000397
dbSNP: rs2228117
Type: single nucleotide variant
Location: chrX:37803981 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 334: the fad-binding fr-type domain; a cross-link site

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 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
CYBB p.Ala156Thr 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/cybb-p-lys334 (accessed [today's date]).

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