Is CYBA p.Ala172= (c.516T>G) pathogenic?

CYBA p.Ala172= (c.516T>G) is classified Likely benign in CYBA (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-05). Very rare (popmax 0.00139%, afr); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative.

How common is CYBA p.Ala172= (c.516T>G) in the general population?

CYBA p.Ala172= (c.516T>G) is very rare (popmax 0.00139%, afr) (gnomAD).

How is Chronic granulomatous disease inherited?

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

CYBA p.Ala172=

Q: What condition is associated with CYBA p.Ala172= (c.516T>G)?

CYBA p.Ala172= (c.516T>G) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-negative, chronic granulomatous disease (ClinVar).

c.516T>G · rs1907154868 · VCV989973

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -1.8
Overall
CADD	1.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00139% African / African-American · 1/71,908 alleles

Overall 0.00013% 2/1,534,788 alleles · very rare exomes 2/1,382,628 · genomes 0/152,160 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00168%	59,546
African / African-Americangrpmax	0.00139%	71,908

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala172=
Coding: c.516T>G
MANE Select: NM_000101
dbSNP: rs1907154868
Type: single nucleotide variant
Location: chr16:88643425 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 172: 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

Also linked: chronic granulomatous disease

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.Ala172Gly 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
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-ala172 (accessed [today's date]).

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