EGR2 p.Val280=
c.840G>C · rs563282095 · VCV696509
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0283%, 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 0.078 | GERP -0.6, phastCons 0.002 |
| Overall | ||
| CADD | 2.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0283%
Admixed American · 17/59,996 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00632%
102/1,613,236 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0283% | 3,529 |
| European (non-Finnish) | 0.00678% | 14,745 |
| African / African-American | 0.00401% | 24,969 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
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.Val280=
- Coding
- c.840G>C
- MANE Select
- NM_000399
- dbSNP
- rs563282095
- Type
- single nucleotide variant
- Location
- chr10:62813798 (GRCh38)
- Gene constraint
- LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.02
- Residue 280
- 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-val280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown