Is CYBB p.Ala368Val (c.1103C>T) pathogenic?

CYBB p.Ala368Val (c.1103C>T) is classified Conflicting classifications of pathogenicity in CYBB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-15). AlphaMissense: likely benign (0.0889); Very rare (popmax 0.00219%, amr); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Ala368Val (c.1103C>T)?

CYBB p.Ala368Val (c.1103C>T) is associated with granulomatous disease, chronic, X-linked, primary ciliary dyskinesia (ClinVar).

How common is CYBB p.Ala368Val (c.1103C>T) in the general population?

CYBB p.Ala368Val (c.1103C>T) is very rare (popmax 0.00219%, 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.Ala368Val (c.1103C>T)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

CYBB p.Ala368Val

c.1103C>T · rs781935760 · VCV635006

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.549	indeterminate
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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	23.9	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 0.00219% Admixed American · 1/45,626 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000579% 7/1,208,806 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,626
Remaining individualsnot grpmax-eligible	0.0021%	47,546
European (non-Finnish)	0.000559%	178,928

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.Ala368Val
Coding: c.1103C>T
MANE Select: NM_000397
dbSNP: rs781935760
Type: single nucleotide variant
Location: chrX:37804082 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 368: the fad-binding fr-type domain; an α-helix

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: primary ciliary dyskinesia

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.Ala368= Likely benign ★ same residue
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-ala368val (accessed [today's date]).

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