Is EGR2 p.Pro47Ser (c.139C>T) pathogenic?

EGR2 p.Pro47Ser (c.139C>T) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.2794); Very rare (popmax 0.004%, afr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with EGR2 p.Pro47Ser (c.139C>T)?

EGR2 p.Pro47Ser (c.139C>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Pro47Ser (c.139C>T) in the general population?

EGR2 p.Pro47Ser (c.139C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about EGR2 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.2794) — an in-silico prediction, not a clinical call.

EGR2 p.Pro47Ser

c.139C>T · rs778369129 · VCV845788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
AlphaMissense	0.2794	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,634 bp · p 0.17 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,934 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,216 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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_000399
dbSNP: rs778369129
Type: single nucleotide variant
Location: chr10:62815891 (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.Pro47Ala Uncertain significance ★★ ⚠ same residue
EGR2 p.Pro47Leu 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

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-pro47ser (accessed [today's date]).

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