Is CYBB p.Lys438Arg (c.1313A>G) pathogenic?

CYBB p.Lys438Arg (c.1313A>G) is classified Likely benign in CYBB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-06). AlphaMissense: likely benign (0.1167); Ultra-rare (popmax 0.0437%, amr); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Lys438Arg (c.1313A>G)?

CYBB p.Lys438Arg (c.1313A>G) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Lys438Arg (c.1313A>G) in the general population?

CYBB p.Lys438Arg (c.1313A>G) is ultra-rare (popmax 0.0437%, amr) (gnomAD).

How is Chronic granulomatous disease inherited?

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

What do computational predictors say about CYBB p.Lys438Arg (c.1313A>G)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

CYBB p.Lys438Arg

c.1313A>G · rs1011161694 · VCV1081893

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0437%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.737	pathogenic-leaning
SaProt	LLR -6.38	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 9,586 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0437% Admixed American · 20/45,728 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0242%

Overall 0.00207% 25/1,208,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0437%	2,286
European (non-Finnish)	0.000559%	178,834

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.Lys438Arg
Coding: c.1313A>G
MANE Select: NM_000397
dbSNP: rs1011161694
Type: single nucleotide variant
Location: chrX:37805167 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 438: a β-strand

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

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.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
CYBB p.Ala57Glu 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-lys438arg (accessed [today's date]).

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