NEFL p.Ser28=
c.84C>T · rs2486888466 · VCV3050755
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.51e-05%, nfe)
Conditions
1
NEFL-related disorder
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 5.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 20.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.51e-05%
European (non-Finnish) · 1/1,175,714 alleles
Overall
6.24e-05%
1/1,603,526 alleles · very rare
exomes 1/1,451,290 · genomes 0/152,236 · joint denominator
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.Ser28=
- Coding
- c.84C>T
- MANE Select
- NM_006158
- dbSNP
- rs2486888466
- Type
- single nucleotide variant
- Location
- chr8:24956432 (GRCh38)
- Gene constraint
- LOEUF 0.986 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.66
- Residue 28
- the 'head' region
Disease context
NEFL-related disorder
Similar variants
- NEFL p.Asn98His Likely pathogenic ★★ same condition
- NEFL p.Tyr265Cys Likely pathogenic ★★ ⚠ same condition
- NEFL p.Glu90Ala Likely pathogenic ★ same condition
- NEFL p.Leu268Arg Likely pathogenic ★ same condition
- NEFL p.Leu94Pro Likely pathogenic ★ same condition
- NEFL p.Leu94Phe Uncertain significance ★ ⚠ same condition
- NEFL p.Glu168= Likely benign same condition
- NEFL p.Leu94= Likely benign 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-ser28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown