Is CYBA p.Ala117Val (c.350C>T) pathogenic?

CYBA p.Ala117Val (c.350C>T) is classified Uncertain significance in CYBA (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-28). AlphaMissense: likely pathogenic (0.9494); Very rare (popmax 0.00382%, amr); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

What condition is associated with CYBA p.Ala117Val (c.350C>T)?

CYBA p.Ala117Val (c.350C>T) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (ClinVar).

How common is CYBA p.Ala117Val (c.350C>T) in the general population?

CYBA p.Ala117Val (c.350C>T) is very rare (popmax 0.00382%, amr) (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.Ala117Val (c.350C>T)?

AlphaMissense predicts likely pathogenic (score 0.9494) — an in-silico prediction, not a clinical call.

CYBA p.Ala117Val

c.350C>T · rs868210009 · VCV655008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00382%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9494	likely pathogenic
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 7,657 bp · p 0.00077 · regional, not allelic
Overall
CADD	28.5	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 0.00382% Admixed American · 2/52,318 alleles

Filtering AF 0.000634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000237%

Overall 0.000498% 7/1,404,728 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00382%	26,159
Finnishnot grpmax-eligible	0.00175%	57,254
European (non-Finnish)	0.000347%	288,035

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.Ala117Val
Coding: c.350C>T
MANE Select: NM_000101
dbSNP: rs868210009
Type: single nucleotide variant
Location: chr16:88646135 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 117: an α-helix

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.Ala117= Likely benign ★★ same residue
CYBA p.Ala117Glu Uncertain significance ★ ⚠ 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

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-ala117val (accessed [today's date]).

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