Is EGR2 p.Pro341Arg (c.1022C>G) pathogenic?

EGR2 p.Pro341Arg (c.1022C>G) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-03). AlphaMissense: ambiguous (0.3742); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with EGR2 p.Pro341Arg (c.1022C>G)?

EGR2 p.Pro341Arg (c.1022C>G) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Pro341Arg (c.1022C>G) in the general population?

EGR2 p.Pro341Arg (c.1022C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGR2 p.Pro341Arg (c.1022C>G)?

AlphaMissense predicts ambiguous (score 0.3742) — an in-silico prediction, not a clinical call.

EGR2 p.Pro341Arg

c.1022C>G · rs1131691827 · VCV1714963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
AlphaMissense	0.3742	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 728 bp · p 0.00043 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EGR2
Protein: p.Pro341Arg
Coding: c.1022C>G
MANE Select: NM_000399
dbSNP: rs1131691827
Type: single nucleotide variant
Location: chr10:62813616 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.02
Residue 341: 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.Pro341Leu Uncertain significance ★★ ⚠ same residue
EGR2 p.Pro341Ser 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-pro341arg (accessed [today's date]).

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