CYBC1 p.Thr139=
c.417G>A · rs772193650 · VCV1925803
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.041 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP -3.3, phastCons 0.77 |
| Overall | ||
| CADD | 6.653 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,080 alleles
Filtering AF
0.00615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00573%
Overall
0.00583%
94/1,612,948 alleles · ultra-rare
exomes 92/1,460,724 · genomes 2/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,080 |
| European (non-Finnish) | 0.00746% | 13,402 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
| East Asian | 0.00223% | 44,888 |
| African / African-American | 0.00133% | 74,932 |
| South Asian | 0.0011% | 91,020 |
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
- CYBC1
- Protein
- p.Thr139=
- Coding
- c.417G>A
- MANE Select
- NM_001033046
- dbSNP
- rs772193650
- Type
- single nucleotide variant
- Location
- chr17:82444473 (GRCh38)
- Gene constraint
- LOEUF 1.556 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.65 · 1 PDB
- Residue 139
- a UniProt-annotated variant site (in cgd5; loss of protein expression; decreased pma-induced oxidative burst in neutrophils)
Similar variants
- CYBC1 p.Thr139Ala Uncertain significance ★ ⚠ same residue
- CYBC1 p.Thr139Met Uncertain significance ★ ⚠ same residue
- CYBC1 p.Arg129Trp Uncertain significance ★★ same type
- CYBC1 p.Arg147Cys Uncertain significance ★★ ⚠ same type
- CYBC1 p.Asp43Asn Uncertain significance ★★ ⚠ same type
- CYBC1 p.Asp98Asn Uncertain significance ★★ ⚠ same type
- CYBC1 p.Thr82Met Uncertain significance ★★ ⚠ same type
- CYBC1 c.127+13C>A Benign/Likely benign ★★ 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/cybc1-p-thr139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown