CYB5A p.Pro96=
c.288G>A · rs7238987 · VCV1600597
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 23.3%, amr) — too common for a highly-penetrant pathogenic allele
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 3.9 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 21.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
23.3%
Admixed American · 13,974/59,996 alleles
Filtering AF
23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 22.8%
Overall
15.9%
256,107/1,608,572 alleles · common
exomes 232,796/1,456,476 · genomes 23,311/152,096 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 23.3% | 4 |
| Finnishnot grpmax-eligible | 17.2% | 6 |
| European (non-Finnish) | 16.2% | 6 |
| Remaining individualsnot grpmax-eligible | 14.7% | 7 |
| South Asian | 14.4% | 7 |
| African / African-American | 14.4% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 9.78% | 10 |
| East Asian | 8.28% | 12 |
| Middle Eastern | 7.5% | 13 |
| Amishnot grpmax-eligible | 4.28% | 23 |
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
- CYB5A
- Protein
- p.Pro96=
- Coding
- c.288G>A
- MANE Select
- NM_148923
- dbSNP
- rs7238987
- Type
- single nucleotide variant
- Location
- chr18:74260915 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI 0.04 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.64 · 1 PDB
- Residue 96
- a UniProt-annotated variant site (in metag); a β-strand
Similar variants
- CYB5A p.Ile81Thr Uncertain significance ★★ ⚠ same type
- CYB5A p.Pro86Ser Uncertain significance ★★ same type
- CYB5A c.129+11G>T Benign ★★ same type
- CYB5A c.130-13C>A Benign ★★ same type
- CYB5A p.Tyr12= Benign ★★ same type
- CYB5A p.His44Leu Likely pathogenic ★ same type
- CYB5A p.Trp27Ter Likely pathogenic ★ same type
- CYB5A c.258+3A>C 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/cyb5a-p-pro96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown