Is EGR2 p.Pro169fs (c.504del) pathogenic?

EGR2 p.Pro169fs (c.504del) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with EGR2 p.Pro169fs (c.504del)?

EGR2 p.Pro169fs (c.504del) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Pro169fs (c.504del) in the general population?

EGR2 p.Pro169fs (c.504del) is absent from gnomAD (gnomAD).

EGR2 p.Pro169fs

c.504del · rs2492299640 · VCV2810022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	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 · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EGR2
Protein: p.Pro169fs
Coding: c.504del
MANE Select: NM_000399
dbSNP: rs2492299640
Type: Deletion
Location: chr10:62814134 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.02
Residue 169: the 'disordered' region

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.Pro169= Likely benign ★★ same residue
EGR2 p.Pro169Leu Uncertain significance ★ ⚠ same residue
EGR2 p.Pro169Ser Uncertain significance ★ ⚠ same residue
EGR2 p.Ala128_Ser129del Uncertain significance ★ same condition
EGR2 p.Lys424fs Uncertain significance ★ same condition
EGR2 p.Pro173_Tyr174delinsHis Uncertain significance ★ same condition
EGR2 p.Ser439fs Uncertain significance ★ same condition
EGR2 p.Ser460fs 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-pro169fs (accessed [today's date]).

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