Is CYBB p.Asp517Glu (c.1551T>A) pathogenic?

CYBB p.Asp517Glu (c.1551T>A) is classified Benign/Likely benign in CYBB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.074); Rare (popmax 0.262%, nfe); Associated with granulomatous disease, chronic, X-linked.

What condition is associated with CYBB p.Asp517Glu (c.1551T>A)?

CYBB p.Asp517Glu (c.1551T>A) is associated with granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Asp517Glu (c.1551T>A) in the general population?

CYBB p.Asp517Glu (c.1551T>A) is rare (popmax 0.262%, nfe) (gnomAD).

How is Chronic granulomatous disease inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CYBB p.Asp517Glu (c.1551T>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

CYBB p.Asp517Glu

c.1551T>A · rs151344452 · VCV68385

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.262%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

granulomatous disease, chronic, X-linked

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP 0.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 9,586 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	17.42	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

Grpmax group 0.262% European (non-Finnish) · 2,342/893,759 alleles

Filtering AF 0.253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.208% 2,516/1,207,338 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.262%	382
Remaining individualsnot grpmax-eligible	0.135%	742
South Asian	0.107%	936
Admixed American	0.0483%	2,068
Middle Eastern	0.046%	2,174
Finnishnot grpmax-eligible	0.0258%	3,873
African / African-American	0.0227%	4,398
East Asian	0.00297%	33,725

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.Asp517Glu
Coding: c.1551T>A
MANE Select: NM_000397
dbSNP: rs151344452
Type: single nucleotide variant
Location: chrX:37809656 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 517: a UniProt-annotated variant site (in); an α-helix

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 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
CYBB p.Ala57Glu 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-asp517glu (accessed [today's date]).

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