Is CYBA p.Pro183Arg (c.548C>G) pathogenic?

CYBA p.Pro183Arg (c.548C>G) is classified Uncertain significance in CYBA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely benign (0.104); Very rare (popmax 0.00149%, nfe); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Pro183Arg (c.548C>G)?

CYBA p.Pro183Arg (c.548C>G) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Pro183Arg (c.548C>G) in the general population?

CYBA p.Pro183Arg (c.548C>G) is very rare (popmax 0.00149%, 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 CYBA p.Pro183Arg (c.548C>G)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

CYBA p.Pro183Arg

c.548C>G · rs939664876 · VCV1416070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00149%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.642	indeterminate
SaProt	LLR -7.75	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 8.3	GERP 0.36, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 7,657 bp · p 0.00077 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00149% European (non-Finnish) · 17/1,143,116 alleles

Filtering AF 0.000906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000741%

Overall 0.00111% 17/1,534,032 alleles · very rare exomes 15/1,381,928 · genomes 2/152,104 · joint denominator

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.Pro183Arg
Coding: c.548C>G
MANE Select: NM_000101
dbSNP: rs939664876
Type: single nucleotide variant
Location: chr16:88643393 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 183: the 'disordered' region

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

Disease context

granulomatous disease, chronic, autosomal recessive, cytochrome b-negative — 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

CYBA p.Pro183= Likely benign ★ 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
CYBA c.288-1G>T Pathogenic/Likely pathogenic ★★ same condition
CYBA c.369+1G>A Likely pathogenic ★★ same condition
CYBA c.58+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-pro183arg (accessed [today's date]).

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