NAXE p.Ile217=
c.651C>T · rs139281973 · VCV1156549
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, 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 -3.4 | GERP -3.4 |
| Overall | ||
| CADD | 11.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
Middle Eastern · 4/6,060 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.0122%
197/1,614,148 alleles · ultra-rare
exomes 179/1,461,876 · genomes 18/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.066% | 1,515 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Admixed American | 0.0217% | 4,618 |
| European (non-Finnish) | 0.0135% | 7,422 |
| South Asian | 0.00329% | 30,361 |
| African / African-American | 0.00267% | 37,512 |
| East Asian | 0.00223% | 44,870 |
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
- NAXE
- Protein
- p.Ile217=
- Coding
- c.651C>T
- MANE Select
- NM_144772
- dbSNP
- rs139281973
- Type
- single nucleotide variant
- Location
- chr1:156593542 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.71
- Residue 217
- a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy and developmental delay; uncertain significance); the yjef n-terminal domain
Similar variants
- NAXE c.664+2T>A Likely pathogenic ★★ same type
- NAXE p.Ser43Ter Pathogenic ★★ same type
- NAXE p.Arg197Gln Uncertain significance ★★ ⚠ same type
- NAXE p.Arg254Cys Uncertain significance ★★ same type
- NAXE p.Glu64Ala Uncertain significance ★★ ⚠ same type
- NAXE p.Leu86Pro Uncertain significance ★★ ⚠ same type
- NAXE p.Ser79Arg Uncertain significance ★★ ⚠ same type
- NAXE p.Val68Leu 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/naxe-p-ile217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown