Is CYBB p.Cys244Ser (c.731G>C) pathogenic?

CYBB p.Cys244Ser (c.731G>C) is classified Pathogenic in CYBB (ClinVar, No assertion criteria, 2 submitters; last evaluated 1991-06-01). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1; Associated with Granulomatous disease, chronic, X-linked, variant.

What condition is associated with CYBB p.Cys244Ser (c.731G>C)?

CYBB p.Cys244Ser (c.731G>C) is associated with Granulomatous disease, chronic, X-linked, variant (ClinVar).

How common is CYBB p.Cys244Ser (c.731G>C) in the general population?

CYBB p.Cys244Ser (c.731G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Cys244Ser (c.731G>C)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

CYBB p.Cys244Ser

c.731G>C · rs137854589 · VCV10924

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Granulomatous disease, chronic, X-linked, variant

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic ✓ concordant with ClinVar · top 6% in CYBB
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -13.65	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 9.9	GERP 1.3, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 5,249 bp · p 0.15 · regional, not allelic
Overall
CADD	23.2	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.Cys244Ser
Coding: c.731G>C
MANE Select: NM_000397
dbSNP: rs137854589
Type: single nucleotide variant
Location: chrX:37799011 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 244: an α-helix; the ferric oxidoreductase domain; a UniProt-annotated variant site (in cgdx)

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

Disease context

Granulomatous disease, chronic, X-linked, variant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYBB p.Cys244Arg Uncertain significance ★ ⚠ same residue
CYBB p.Gly389Ala Pathogenic same condition
CYBB p.His303Asn Pathogenic same condition
CYBB c.1151+2T>C Pathogenic ★★ same type
CYBB c.1315-2A>G Pathogenic/Likely pathogenic ★★ same type
CYBB c.141+1G>T Pathogenic ★★ same type
CYBB c.252+5G>A Pathogenic ★★ same type
CYBB c.483+1G>A Pathogenic ★★ same type

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-cys244ser (accessed [today's date]).

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