NOBOX p.Pro328=
c.984C>T · VCV4898303
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00122%, sas)
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 0.25 | GERP -2, phastCons 0.94 |
| Overall | ||
| CADD | 4.463 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00122%
South Asian · 1/81,706 alleles
Filtering AF
9.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.7e-05%
Overall
0.00033%
4/1,210,528 alleles · very rare
exomes 4/1,059,090 · genomes 0/151,438 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00122% | 81,706 |
| European (non-Finnish) | 0.000368% | 271,745 |
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.Pro328=
- Coding
- c.984C>T
- MANE Select
- NM_001436401
- Type
- single nucleotide variant
- Location
- chr7:144399084 (GRCh38)
- Gene constraint
- LOEUF 1.061 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.12
- Residue 328
- a DNA-binding 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-pro328 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown