NEFH p.Ile245=
c.735C>T · rs1009478060 · VCV740384
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0472%, amr)
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 0.33 | GERP 1.1, phastCons 0.99 |
| Overall | ||
| CADD | 14.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0472%
Admixed American · 24/50,886 alleles
Filtering AF
0.0325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0277%
Overall
0.00268%
41/1,532,018 alleles · ultra-rare
exomes 21/1,379,738 · genomes 20/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0472% | 2,120 |
| Remaining individualsnot grpmax-eligible | 0.0151% | 6,640 |
| East Asian | 0.00983% | 10,173 |
| African / African-American | 0.00137% | 72,742 |
| South Asian | 0.00119% | 83,862 |
| European (non-Finnish) | 0.000175% | 572,770 |
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
- NEFH
- Protein
- p.Ile245=
- Coding
- c.735C>T
- MANE Select
- NM_021076
- dbSNP
- rs1009478060
- Type
- single nucleotide variant
- Location
- chr22:29480997 (GRCh38)
- Gene constraint
- LOEUF 1.417 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 245
- the if rod domain; the 'linker 12' region
Similar variants
- NEFH p.Ile245Ser Uncertain significance ★★ same residue
- NEFH c.1208+4A>T Uncertain significance ★★ same type
- NEFH c.1209-2A>G Uncertain significance ★★ same type
- NEFH p.Ala103Thr Uncertain significance ★★ same type
- NEFH p.Ala141Thr Uncertain significance ★★ same type
- NEFH p.Ala189Val Uncertain significance ★★ same type
- NEFH p.Ala195Thr Uncertain significance ★★ same type
- NEFH p.Ala203Thr 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/nefh-p-ile245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown