Is CYB561 p.Ala8= (c.24C>T) pathogenic?

CYB561 p.Ala8= (c.24C>T) is classified Likely benign in CYB561 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-07). Rare (popmax 0.253%, nfe); Associated with CYB561-related disorder.

What condition is associated with CYB561 p.Ala8= (c.24C>T)?

CYB561 p.Ala8= (c.24C>T) is associated with CYB561-related disorder (ClinVar).

How common is CYB561 p.Ala8= (c.24C>T) in the general population?

CYB561 p.Ala8= (c.24C>T) is rare (popmax 0.253%, nfe) (gnomAD).

CYB561 p.Ala8=

c.24C>T · rs140356224 · VCV3060907

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.253%, nfe)

Conditions

CYB561-related disorder

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 -0.028	GERP -3.9
Overall
CADD	2.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.253% European (non-Finnish) · 2,985/1,179,872 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.242%

Overall 0.207% 3,329/1,611,874 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.253%	395
Remaining individualsnot grpmax-eligible	0.211%	473
Admixed American	0.13%	769
Middle Eastern	0.121%	828
Finnishnot grpmax-eligible	0.0738%	1,355
South Asian	0.0472%	2,118
African / African-American	0.0466%	2,144
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,858

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: CYB561
Protein: p.Ala8=
Coding: c.24C>T
MANE Select: NM_001915
dbSNP: rs140356224
Type: single nucleotide variant
Location: chr17:63437524 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 93.13

Full CYB561 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CYB561-related disorder

Similar variants

CYB561 c.-13-2648G>A Benign same condition
CYB561 p.Asn202= Likely benign same condition
CYB561 p.Leu187= Likely benign same condition
CYB561 p.Leu69= Benign same condition
CYB561 p.Phe106= Likely benign same condition
CYB561 p.Ala104Val Uncertain significance ★ same type
CYB561 p.Ala115Thr Uncertain significance ★ ⚠ same type
CYB561 p.Ala193Ser Uncertain significance ★ ⚠ same type

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/cyb561-p-ala8 (accessed [today's date]).

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