Is CYBB p.Ala233Val (c.698C>T) pathogenic?

CYBB p.Ala233Val (c.698C>T) is classified Conflicting classifications of pathogenicity in CYBB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-08). AlphaMissense: likely benign (0.0985); Very rare (popmax 0.000224%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CYBB p.Ala233Val (c.698C>T)?

CYBB p.Ala233Val (c.698C>T) is associated with Inborn genetic diseases, granulomatous disease, chronic, X-linked, chronic granulomatous disease (ClinVar).

How common is CYBB p.Ala233Val (c.698C>T) in the general population?

CYBB p.Ala233Val (c.698C>T) is very rare (popmax 0.000224%, nfe) (gnomAD).

What do computational predictors say about CYBB p.Ala233Val (c.698C>T)?

AlphaMissense predicts likely benign (score 0.0985) — an in-silico prediction, not a clinical call.

CYBB p.Ala233Val

c.698C>T · rs782174347 · VCV1017273

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0985	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -3	GERP -2.6
Regional constraint	o/e 1.17	unconstrained · MANE · 5,249 bp · p 0.15 · regional, not allelic
Overall
CADD	0.003	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 0.000224% European (non-Finnish) · 2/892,879 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000166% 2/1,206,584 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.Ala233Val
Coding: c.698C>T
MANE Select: NM_000397
dbSNP: rs782174347
Type: single nucleotide variant
Location: chrX:37798978 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 233: an α-helix; the ferric oxidoreductase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: granulomatous disease, chronic, X-linked chronic granulomatous disease

Similar variants

CYBB p.Ala233Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala233val (accessed [today's date]).

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