NAXE p.Lys58=
c.174G>A · rs1173030441 · VCV1951593
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 1.8 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,876 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00031%
5/1,613,368 alleles · very rare
exomes 5/1,461,046 · genomes 0/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,876 |
| European (non-Finnish) | 0.000339% | 294,943 |
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.Lys58=
- Coding
- c.174G>A
- MANE Select
- NM_144772
- dbSNP
- rs1173030441
- Type
- single nucleotide variant
- Location
- chr1:156591978 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.71
- Residue 58
- a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy and developmental delay; uncertain significance)
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-lys58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown