Is CYBB p.Pro528fs (c.1580_1581dup) pathogenic?

CYBB p.Pro528fs (c.15801581dup) is classified Likely pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-17). Associated with CYBB-related disorders.

What condition is associated with CYBB p.Pro528fs (c.1580_1581dup)?

CYBB p.Pro528fs (c.1580_1581dup) is associated with CYBB-related disorders (ClinVar).

CYBB p.Pro528fs

c.1580_1581dup · VCV4949674

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

CYBB-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 9 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CYBB
Protein: p.Pro528fs
Coding: c.1580_1581dup
MANE Select: NM_000397
Type: Microsatellite
Location: chrX:37809682 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB

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

Disease context

CYBB-related disorders

Similar variants

CYBB c.252+5G>A Pathogenic ★★ same condition
CYBB p.Ala156Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYBB p.Ala84= Pathogenic ★★ same condition
CYBB p.Arg226Ter Pathogenic ★★ same condition
CYBB p.Arg290Ter Pathogenic ★★ same condition
CYBB p.Arg73Ter Pathogenic ★★ same condition
CYBB p.Arg91Ter Pathogenic ★★ same condition
CYBB p.Gly408Glu 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-pro528fs (accessed [today's date]).

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