NEFH p.Pro595=
c.1785G>A · rs766633327 · VCV1554002
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00661%, sas)
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 -8.7 | GERP -3.1 |
| Overall | ||
| CADD | 1.523 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00661%
South Asian · 6/90,744 alleles
Filtering AF
0.00287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00196%
Overall
0.00112%
18/1,607,206 alleles · very rare
exomes 17/1,461,484 · genomes 1/145,722 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00661% | 15,124 |
| Admixed American | 0.00169% | 59,266 |
| European (non-Finnish) | 0.000933% | 107,145 |
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.Pro595=
- Coding
- c.1785G>A
- MANE Select
- NM_021076
- dbSNP
- rs766633327
- Type
- single nucleotide variant
- Location
- chr22:29489425 (GRCh38)
- Gene constraint
- LOEUF 1.417 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 595
- the 'tail' region; the 'disordered' region; the '30 x 6 aa repeats of k-s-p-[aepv]-[eak]-[aevk]' region
Similar variants
- NEFH p.Pro595Leu Uncertain significance ★★ same residue
- NEFH p.Pro595Ser Benign/Likely benign ★★ 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
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-pro595 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown