Is EGR2 p.Ser439Phe (c.1316C>T) pathogenic?

EGR2 p.Ser439Phe (c.1316C>T) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-20). AlphaMissense: ambiguous (0.5204); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with EGR2 p.Ser439Phe (c.1316C>T)?

EGR2 p.Ser439Phe (c.1316C>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is EGR2 p.Ser439Phe (c.1316C>T) in the general population?

EGR2 p.Ser439Phe (c.1316C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGR2 p.Ser439Phe (c.1316C>T)?

AlphaMissense predicts ambiguous (score 0.5204) — an in-silico prediction, not a clinical call.

EGR2 p.Ser439Phe

c.1316C>T · rs1842160008 · VCV2128347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5204 · 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	0.5204	ambiguous
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.91	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 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 158 bp · p 0.87 · regional, not allelic
Overall
CADD	22.6	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.Ser439Phe
Coding: c.1316C>T
MANE Select: NM_000399
dbSNP: rs1842160008
Type: single nucleotide variant
Location: chr10:62813322 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.02
Residue 439: 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.Ser439fs 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
EGR2 p.Glu356Gln 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-ser439phe (accessed [today's date]).

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