Is EGR2 p.Pro169= (c.507G>A) pathogenic?

EGR2 p.Pro169= (c.507G>A) is classified Likely benign in EGR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-15). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with EGR2 p.Pro169= (c.507G>A)?

EGR2 p.Pro169= (c.507G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Pro169= (c.507G>A) in the general population?

EGR2 p.Pro169= (c.507G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

EGR2 p.Pro169=

c.507G>A · rs1060504688 · VCV415907

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

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 -7.8	GERP -4.7
Overall
CADD	6.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,814 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,576 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,814
European (non-Finnish)	0.000932%	107,254

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.Pro169=
Coding: c.507G>A
MANE Select: NM_000399
dbSNP: rs1060504688
Type: single nucleotide variant
Location: chr10:62814131 (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

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

Also linked: Charcot-Marie-Tooth disease type 1

Similar variants

EGR2 p.Pro169Leu Uncertain significance ★ ⚠ same residue
EGR2 p.Pro169Ser Uncertain significance ★ ⚠ same residue
EGR2 p.Pro169fs 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-pro169 (accessed [today's date]).

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