NONO p.Pro421=
c.1263G>A · rs141184952 · VCV1960123
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0124%, 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 |
|---|---|---|
| Pangolin | Δ0.21 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.035 | GERP -4.1, phastCons 0.001 |
| Overall | ||
| CADD | 5.021 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0124%
South Asian · 7/56,514 alleles
Filtering AF
0.00573%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00409%
Overall
0.00174%
21/1,205,401 alleles · ultra-rare
exomes 21/1,091,525 · genomes 0/113,876 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0124% | 8,073 |
| African / African-American | 0.00519% | 19,259 |
| Remaining individualsnot grpmax-eligible | 0.00422% | 23,720 |
| Admixed American | 0.00218% | 45,909 |
| European (non-Finnish) | 0.000899% | 111,261 |
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
- NONO
- Protein
- p.Pro421=
- Coding
- c.1263G>A
- MANE Select
- NM_007363
- dbSNP
- rs141184952
- Type
- single nucleotide variant
- Location
- chrX:71298798 (GRCh38)
- Structure
- AlphaFold pLDDT 77.76 · 9 PDB
Similar variants
- NONO c.651-1G>C Likely pathogenic ★★ same type
- NONO p.Ala377= Pathogenic ★★ same type
- NONO p.Arg184Ter Pathogenic ★★ same type
- NONO p.Ala453Pro Uncertain significance ★★ ⚠ same type
- NONO p.Arg202Trp Uncertain significance ★★ ⚠ same type
- NONO p.Arg456Ser Uncertain significance ★★ ⚠ same type
- NONO p.Asn161Asp Uncertain significance ★★ ⚠ same type
- NONO p.Gln380Arg 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/nono-p-pro421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown