Is CYBB p.Glu402Asp (c.1206G>T) pathogenic?

CYBB p.Glu402Asp (c.1206G>T) is classified Uncertain significance in CYBB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0905); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CYBB p.Glu402Asp (c.1206G>T)?

CYBB p.Glu402Asp (c.1206G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CYBB p.Glu402Asp (c.1206G>T) in the general population?

CYBB p.Glu402Asp (c.1206G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Glu402Asp (c.1206G>T)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

CYBB p.Glu402Asp

c.1206G>T · rs2519209755 · VCV2631836

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.727	pathogenic-leaning
SaProt	LLR -9.68	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 9,586 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	20.8	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.Glu402Asp
Coding: c.1206G>T
MANE Select: NM_000397
dbSNP: rs2519209755
Type: single nucleotide variant
Location: chrX:37805060 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 402: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYBB p.Ala224Ser Uncertain significance ★★ ⚠ same condition
CYBB p.Asn128Lys Uncertain significance ★★ ⚠ same condition
CYBB p.Gly166Asp Uncertain significance ★★ ⚠ same condition
CYBB p.His449Arg Uncertain significance ★★ ⚠ same condition
CYBB p.Ile221Thr Uncertain significance ★★ ⚠ same condition
CYBB p.Ser87Leu Uncertain significance ★★ ⚠ same condition
CYBB p.Thr242Arg Uncertain significance ★★ ⚠ same condition
CYBB p.Val181Ala 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-glu402asp (accessed [today's date]).

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