Is CYBB p.Val534Ile (c.1600G>A) pathogenic?

CYBB p.Val534Ile (c.1600G>A) is classified Uncertain significance in CYBB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-31). AlphaMissense: likely benign (0.1247); Very rare (popmax 0.000897%); Associated with chronic granulomatous disease.

What condition is associated with CYBB p.Val534Ile (c.1600G>A)?

CYBB p.Val534Ile (c.1600G>A) is associated with chronic granulomatous disease (ClinVar).

How common is CYBB p.Val534Ile (c.1600G>A) in the general population?

CYBB p.Val534Ile (c.1600G>A) is very rare (popmax 0.000897%) (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.Val534Ile (c.1600G>A)?

AlphaMissense predicts likely benign (score 0.1247) — an in-silico prediction, not a clinical call.

CYBB p.Val534Ile

c.1600G>A · VCV4065622

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000897%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chronic granulomatous disease

Computational evidence

Protein change
AlphaMissense	0.1247	likely benign
REVEL	0.733	pathogenic-leaning
SaProt	LLR -9.65	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 9,586 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	25.7	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 0.000897%

Overall 0.000897% 1/111,471 alleles · very rare

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.Val534Ile
Coding: c.1600G>A
MANE Select: NM_000397
Type: single nucleotide variant
Location: chrX:37810804 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 534: a UniProt-annotated variant site (in cgdx); a β-strand

Full CYBB 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

CYBB p.Val534Asp Uncertain significance ⚠ same residue
CYBB c.1151+2T>C Pathogenic ★★ same condition
CYBB c.483+1G>T Pathogenic ★★ same condition
CYBB c.483+3A>T Likely pathogenic ★★ same condition
CYBB p.Arg226Ter Pathogenic ★★ same condition
CYBB p.Glu203Ter Pathogenic/Likely pathogenic ★★ same condition
CYBB p.Ala417Thr Uncertain significance ★★ ⚠ same condition
CYBB p.Ala431Thr Uncertain significance ★★ ⚠ 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-val534ile (accessed [today's date]).

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