Is EGR2 p.Ala308= (c.924C>T) pathogenic?

EGR2 p.Ala308= (c.924C>T) is classified Conflicting classifications of pathogenicity in EGR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-03-03). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with EGR2 p.Ala308= (c.924C>T)?

EGR2 p.Ala308= (c.924C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1D, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Ala308= (c.924C>T) in the general population?

EGR2 p.Ala308= (c.924C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

EGR2 p.Ala308=

c.924C>T · rs886047093 · VCV300276

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -5.2
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,856 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,610,716 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,856
European (non-Finnish)	0.00153%	65,520
African / African-American	0.00134%	74,850

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.Ala308=
Coding: c.924C>T
MANE Select: NM_000399
dbSNP: rs886047093
Type: single nucleotide variant
Location: chr10:62813714 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

EGR2 p.Ala308Thr Uncertain significance ★★ ⚠ same residue
EGR2 p.Ala308_Ala309dup Uncertain significance ★★ same residue
EGR2 p.Ala308_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

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-ala308 (accessed [today's date]).

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