Is EGR2 p.Ala307= (c.921C>T) pathogenic?

EGR2 p.Ala307= (c.921C>T) is classified Likely benign in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with EGR2 p.Ala307= (c.921C>T)?

EGR2 p.Ala307= (c.921C>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Ala307= (c.921C>T) in the general population?

EGR2 p.Ala307= (c.921C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

EGR2 p.Ala307=

c.921C>T · rs751393520 · VCV1125493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.5	GERP -5.2
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00279% 45/1,611,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.00356%	28,083
Remaining individualsnot grpmax-eligible	0.00321%	31,148

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.Ala307=
Coding: c.921C>T
MANE Select: NM_000399
dbSNP: rs751393520
Type: single nucleotide variant
Location: chr10:62813717 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGR2 p.Ala307_Ala309del Uncertain significance ★ same residue
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

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-ala307 (accessed [today's date]).

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