NYX p.Pro396=
c.1188G>A · rs139558261 · VCV96087
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.429%, afr)
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 -3.2 | GERP -3.8 |
| Overall | ||
| CADD | 0.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.429%
African / African-American · 244/56,934 alleles
Filtering AF
0.384%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.367%
Overall
0.0228%
273/1,197,416 alleles · rare
exomes 133/1,086,153 · genomes 140/111,263 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.429% | 233 |
| Middle Eastern | 0.0466% | 2,146 |
| Remaining individualsnot grpmax-eligible | 0.0318% | 3,143 |
| Admixed American | 0.0204% | 4,904 |
| South Asian | 0.00183% | 54,788 |
| European (non-Finnish) | 0.000225% | 444,840 |
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
- NYX
- Protein
- p.Pro396=
- Coding
- c.1188G>A
- MANE Select
- NM_001378477
- dbSNP
- rs139558261
- Type
- single nucleotide variant
- Location
- chrX:41474656 (GRCh38)
- Structure
- AlphaFold pLDDT 82.68
Similar variants
- NYX p.Pro396Arg Uncertain significance ★ ⚠ same residue
- NYX p.Asn211Ser Pathogenic/Likely pathogenic ★★ same type
- NYX p.Pro170Arg Pathogenic ★★ same type
- NYX p.Ser196Ter Pathogenic ★★ same type
- NYX p.Ser40Ter Pathogenic/Likely pathogenic ★★ same type
- NYX p.Ala113Thr Uncertain significance ★★ same type
- NYX p.Ala113Val Uncertain significance ★★ same type
- NYX p.Ala123Val 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/nyx-p-pro396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown