NOBOX p.Ser53=
c.159A>C · rs1440135419 · VCV2658133
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0172%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -2.9 |
| Overall | ||
| CADD | 0.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0172%
Middle Eastern · 1/5,830 alleles
Filtering AF
0.00219%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00194%
Overall
0.00236%
37/1,569,674 alleles · ultra-rare
exomes 37/1,417,484 · genomes 0/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0172% | 5,830 |
| European (non-Finnish) | 0.00302% | 33,118 |
| South Asian | 0.00121% | 82,308 |
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
- NOBOX
- Protein
- p.Ser53=
- Coding
- c.159A>C
- MANE Select
- NM_001436401
- dbSNP
- rs1440135419
- Type
- single nucleotide variant
- Location
- chr7:144401476 (GRCh38)
- Gene constraint
- LOEUF 1.061 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.12
Similar variants
- NOBOX p.Arg218Ter Pathogenic ★★ same type
- NOBOX p.Arg142Cys Uncertain significance ★★ ⚠ same type
- NOBOX p.Arg218Gln Uncertain significance ★★ ⚠ same type
- NOBOX p.Arg44Trp Uncertain significance ★★ ⚠ same type
- NOBOX p.Gly26Arg Uncertain significance ★★ ⚠ same type
- NOBOX p.Leu386Val Uncertain significance ★★ ⚠ same type
- NOBOX p.Pro179Leu Uncertain significance ★★ ⚠ same type
- NOBOX p.Pro366Ala 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/nobox-p-ser53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown