EGR2 p.Leu466=
c.1398C>T · rs1483612429 · VCV2715590
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00183%, amr)
Conditions
1
Charcot-Marie-Tooth disease type 1
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 -4.6 | GERP -4.7 |
| Overall | ||
| CADD | 0.233 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00183%
Admixed American · 1/54,568 alleles
Filtering AF
6.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000319%
5/1,567,990 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00183% | 54,568 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,496 |
| European (non-Finnish) | 0.000259% | 386,323 |
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
- EGR2
- Protein
- p.Leu466=
- Coding
- c.1398C>T
- MANE Select
- NM_000399
- dbSNP
- rs1483612429
- Type
- single nucleotide variant
- Location
- chr10:62813240 (GRCh38)
- Gene constraint
- LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.02
- Residue 466
- the 'disordered' region
Similar variants
- EGR2 p.Arg359Trp Pathogenic ★★ same condition
- EGR2 p.Arg381Cys Pathogenic ★★ same condition
- EGR2 p.Arg381His Pathogenic ★★ same condition
- EGR2 p.Arg381Leu Pathogenic ★★ same condition
- EGR2 p.Arg409Gln Pathogenic/Likely pathogenic ★★ same condition
- EGR2 p.Arg409Trp Pathogenic/Likely pathogenic ★★ same condition
- EGR2 p.Glu356Gln Likely pathogenic ★★ ⚠ same condition
- EGR2 p.Glu356Lys 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/egr2-p-leu466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown