NOBOX p.Pro103=
c.309A>G · rs201423277 · VCV778355
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, amr)
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 -8.5 | GERP -2.8 |
| Overall | ||
| CADD | 0.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
Admixed American · 23/59,950 alleles
Filtering AF
0.0262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00198%
32/1,613,580 alleles · ultra-rare
exomes 26/1,461,416 · genomes 6/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0384% | 2,607 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,795 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,613 |
| European (non-Finnish) | 0.000254% | 393,263 |
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.Pro103=
- Coding
- c.309A>G
- MANE Select
- NM_001436401
- dbSNP
- rs201423277
- Type
- single nucleotide variant
- Location
- chr7:144401326 (GRCh38)
- Gene constraint
- LOEUF 1.061 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.12
- Residue 103
- the 'disordered' region
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-pro103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown