Is CYBA p.Arg90Gly (c.268C>G) pathogenic?

CYBA p.Arg90Gly (c.268C>G) is classified Likely pathogenic in CYBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-18). AlphaMissense: likely pathogenic (0.9817); Very rare (popmax 0.00329%, sas); Associated with chronic granulomatous disease.

What condition is associated with CYBA p.Arg90Gly (c.268C>G)?

CYBA p.Arg90Gly (c.268C>G) is associated with chronic granulomatous disease, granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Arg90Gly (c.268C>G) in the general population?

CYBA p.Arg90Gly (c.268C>G) is very rare (popmax 0.00329%, sas) (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 CYBA p.Arg90Gly (c.268C>G)?

AlphaMissense predicts likely pathogenic (score 0.9817) — an in-silico prediction, not a clinical call.

CYBA p.Arg90Gly

c.268C>G · rs179363892 · VCV1522930

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chronic granulomatous disease

Computational evidence

Protein change
AlphaMissense	0.9817	likely pathogenic ✓ concordant with ClinVar
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -13.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.4	GERP 0.26, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 7,657 bp · p 0.00077 · regional, not allelic
Overall
CADD	27.8	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

Grpmax group 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000342% 5/1,461,640 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
European (non-Finnish)	0.00017%	589,960

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: CYBA
Protein: p.Arg90Gly
Coding: c.268C>G
MANE Select: NM_000101
dbSNP: rs179363892
Type: single nucleotide variant
Location: chr16:88646774 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 90: a UniProt-annotated variant site (in cgd4); an α-helix

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

Disease context

chronic granulomatous disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

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

CYBA p.Arg90Gln Pathogenic/Likely pathogenic ★★ same residue
CYBA p.Arg90Trp Pathogenic/Likely pathogenic ★★ same residue
CYBA p.Arg90Pro Likely pathogenic ★ same residue
CYBA p.Arg90fs Pathogenic/Likely pathogenic ★★ same residue
CYBA c.128+2T>C Likely pathogenic ★★ same condition
CYBA c.204-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYBA c.287+1G>T Pathogenic/Likely pathogenic ★★ same condition
CYBA c.287+2T>C 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/cyba-p-arg90gly (accessed [today's date]).

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