Is EGR2 p.Arg362Ter (c.1084C>T) pathogenic?

EGR2 p.Arg362Ter (c.1084C>T) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-05). Very rare (popmax 8.48e-05%, nfe); Associated with Charcot-Marie-Tooth disease type 4E.

What condition is associated with EGR2 p.Arg362Ter (c.1084C>T)?

EGR2 p.Arg362Ter (c.1084C>T) is associated with Charcot-Marie-Tooth disease type 4E, Charcot-Marie-Tooth disease type 3, Charcot-Marie-Tooth disease type 1D (ClinVar).

How common is EGR2 p.Arg362Ter (c.1084C>T) in the general population?

EGR2 p.Arg362Ter (c.1084C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Charcot-Marie-Tooth disease type 4E inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EGR2 p.Arg362Ter

c.1084C>T · rs1554853028 · VCV548617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Charcot-Marie-Tooth disease type 4E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -0.24, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,914 alleles

Overall 6.85e-05% 1/1,460,704 alleles · very rare

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.Arg362Ter
Coding: c.1084C>T
MANE Select: NM_000399
dbSNP: rs1554853028
Type: single nucleotide variant
Location: chr10:62813554 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.02

Full EGR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 4E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 3 Charcot-Marie-Tooth disease type 1D

For Charcot-Marie-Tooth disease type 4E (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

EGR2 p.Arg362= Benign ★★ same residue
EGR2 p.Arg359Trp Pathogenic ★★ same condition
EGR2 p.Arg381Cys Pathogenic ★★ same condition
EGR2 p.Arg381His Pathogenic ★★ same condition
EGR2 p.Arg409Trp Pathogenic/Likely pathogenic ★★ same condition
EGR2 p.Glu412Gly Pathogenic/Likely pathogenic ★★ same condition
EGR2 p.Arg257Gln Uncertain significance ★★ ⚠ same condition
EGR2 p.Asn328Ser Uncertain significance ★★ ⚠ 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-arg362ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown