Is CYBB p.Ile248= (c.744C>T) pathogenic?

CYBB p.Ile248= (c.744C>T) is classified Likely benign in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). Very rare (popmax 0.00438%, amr); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Ile248= (c.744C>T)?

CYBB p.Ile248= (c.744C>T) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Ile248= (c.744C>T) in the general population?

CYBB p.Ile248= (c.744C>T) is very rare (popmax 0.00438%, 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.

CYBB p.Ile248=

c.744C>T · rs190924506 · VCV1093514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00438%, amr)

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP 0.44, phastCons 0.002
Overall
CADD	2.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00438% Admixed American · 2/45,668 alleles

Filtering AF 0.000726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000272%

Overall 0.000829% 10/1,206,610 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00438%	22,834
African / African-American	0.00175%	57,182
European (non-Finnish)	0.000784%	127,473

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.Ile248=
Coding: c.744C>T
MANE Select: NM_000397
dbSNP: rs190924506
Type: single nucleotide variant
Location: chrX:37799024 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 248: an α-helix; the ferric oxidoreductase domain

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

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.Ile248fs Pathogenic ★★ 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-ile248 (accessed [today's date]).

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