NAXE p.Pro199=
c.597G>A · rs148479602 · VCV747124
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.018%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -4.8 |
| Overall | ||
| CADD | 7.679 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.018%
European (non-Finnish) · 212/1,180,030 alleles
Filtering AF
0.016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.0139%
224/1,614,068 alleles · ultra-rare
exomes 217/1,461,886 · genomes 7/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.018% | 5,566 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,810 |
| African / African-American | 0.004% | 24,983 |
| Admixed American | 0.00167% | 60,000 |
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.Pro199=
- Coding
- c.597G>A
- MANE Select
- NM_144772
- dbSNP
- rs148479602
- Type
- single nucleotide variant
- Location
- chr1:156593488 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.71
- Residue 199
- 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-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown