Is CYBB p.Ala84= (c.252G>A) pathogenic?

CYBB p.Ala84= (c.252G>A) is classified Pathogenic in CYBB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-03-31). Absent from gnomAD v4.1; Associated with CYBB-related disorders.

How common is CYBB p.Ala84= (c.252G>A) in the general population?

CYBB p.Ala84= (c.252G>A) is absent from gnomAD v4.1 (gnomAD).

CYBB p.Ala84=

Q: What condition is associated with CYBB p.Ala84= (c.252G>A)?

CYBB p.Ala84= (c.252G>A) is associated with CYBB-related disorders, X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency, granulomatous disease, chronic, X-linked (ClinVar).

c.252G>A · rs387906485 · VCV10933

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,159,292)

Conditions

CYBB-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.77	donor loss · deltas
Pangolin	Δ0.73	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP -0.84, phastCons 1
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,159,292). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CYBB
Protein: p.Ala84=
Coding: c.252G>A
MANE Select: NM_000397
dbSNP: rs387906485
Type: single nucleotide variant
Location: chrX:37783600 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 84: the ferric oxidoreductase domain

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

Disease context

CYBB-related disorders

Also linked: X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency granulomatous disease, chronic, X-linked

Similar variants

CYBB p.Ala84Val Uncertain significance ★★ ⚠ 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-ala84 (accessed [today's date]).

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