NEFL p.Arg107=
c.321C>G · rs1198042093 · VCV533518
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
Charcot-Marie-Tooth disease
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 4.5 | GERP -0.14, phastCons 1 |
| Overall | ||
| CADD | 20.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,744 alleles
Filtering AF
0.000501%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000807%
13/1,610,476 alleles · very rare
exomes 13/1,458,154 · genomes 0/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,744 |
| South Asian | 0.00111% | 90,128 |
| European (non-Finnish) | 0.000933% | 107,146 |
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
- NEFL
- Protein
- p.Arg107=
- Coding
- c.321C>G
- MANE Select
- NM_006158
- dbSNP
- rs1198042093
- Type
- single nucleotide variant
- Location
- chr8:24956195 (GRCh38)
- Gene constraint
- LOEUF 0.986 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.66
- Residue 107
- the if rod domain; the 'coil 1a' region
Similar variants
- NEFL p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
- NEFL p.Arg421Ter Pathogenic ★★ same condition
- NEFL p.Asn98Ser Pathogenic/Likely pathogenic ★★ same condition
- NEFL p.Glu186Ter Pathogenic/Likely pathogenic ★★ same condition
- NEFL p.Glu396Lys Pathogenic ★★ same condition
- NEFL p.Glu90Lys Pathogenic ★★ same condition
- NEFL p.Pro22Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NEFL p.Pro8Leu Pathogenic/Likely pathogenic ★★ same condition
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/nefl-p-arg107 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown