Is EGR2 p.Pro40Ser (c.118C>T) pathogenic?

EGR2 p.Pro40Ser (c.118C>T) is classified Uncertain significance in EGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely pathogenic (0.6652); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EGR2 p.Pro40Ser (c.118C>T)?

EGR2 p.Pro40Ser (c.118C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EGR2 p.Pro40Ser (c.118C>T) in the general population?

EGR2 p.Pro40Ser (c.118C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGR2 p.Pro40Ser (c.118C>T)?

AlphaMissense predicts likely pathogenic (score 0.6652) — an in-silico prediction, not a clinical call.

EGR2 p.Pro40Ser

c.118C>T · VCV4016895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6652 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6652	likely pathogenic
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,634 bp · p 0.17 · regional, not allelic
Overall
CADD	25.7	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.Pro40Ser
Coding: c.118C>T
MANE Select: NM_000399
Type: single nucleotide variant
Location: chr10:62815912 (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

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

Similar variants

EGR2 p.Ala303Pro Uncertain significance ★★ ⚠ same condition
EGR2 p.Ala308Thr Uncertain significance ★★ ⚠ same condition
EGR2 p.Ala399Ser Uncertain significance ★★ ⚠ same condition
EGR2 p.Ala55Ser Uncertain significance ★★ ⚠ same condition
EGR2 p.Arg246Cys Uncertain significance ★★ ⚠ same condition
EGR2 p.Asn41Ser Uncertain significance ★★ ⚠ same condition
EGR2 p.Asp30Asn Uncertain significance ★★ ⚠ same condition
EGR2 p.Glu290Lys 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-pro40ser (accessed [today's date]).

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