Is CYBB p.Gln231Pro (c.692A>C) pathogenic?

CYBB p.Gln231Pro (c.692A>C) is classified Pathogenic in CYBB (ClinVar, No assertion criteria, 3 submitters; last evaluated 2011-03-01). AlphaMissense: likely pathogenic (0.9398); Absent from gnomAD v4.1; Associated with X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency.

How common is CYBB p.Gln231Pro (c.692A>C) in the general population?

CYBB p.Gln231Pro (c.692A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Gln231Pro (c.692A>C)?

AlphaMissense predicts likely pathogenic (score 0.9398) — an in-silico prediction, not a clinical call.

CYBB p.Gln231Pro

Q: What condition is associated with CYBB p.Gln231Pro (c.692A>C)?

CYBB p.Gln231Pro (c.692A>C) is associated with X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency, chronic granulomatous disease (ClinVar).

Q: How is X-linked mendelian susceptibility to mycobacterial diseases inherited?

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

c.692A>C · rs151344498 · VCV29969

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9398 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency

Computational evidence

Protein change
AlphaMissense	0.9398	likely pathogenic ✓ concordant with ClinVar
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -14.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 5,249 bp · p 0.15 · regional, not allelic
Overall
CADD	25.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYBB
Protein: p.Gln231Pro
Coding: c.692A>C
MANE Select: NM_000397
dbSNP: rs151344498
Type: single nucleotide variant
Location: chrX:37798972 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 231: a β-strand; the ferric oxidoreductase domain; a UniProt-annotated variant site (in imd34)

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

Disease context

X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chronic granulomatous disease

For X-linked mendelian susceptibility to mycobacterial diseases (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

CYBB p.Gln231Ter Pathogenic ★ 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.Ala84= Pathogenic ★★ same condition
CYBB p.Arg226Ter Pathogenic ★★ same condition
CYBB p.Glu203Ter Pathogenic/Likely pathogenic ★★ same condition
CYBB p.Ala417Thr 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-gln231pro (accessed [today's date]).

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