Is EN2 p.Gly111Val (c.332G>T) pathogenic?

EN2 p.Gly111Val (c.332G>T) is classified Uncertain significance in EN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0945); Absent from gnomAD v4.1.

How common is EN2 p.Gly111Val (c.332G>T) in the general population?

EN2 p.Gly111Val (c.332G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EN2 p.Gly111Val (c.332G>T)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

EN2 p.Gly111Val

c.332G>T · VCV4664252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,341,522)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Pangolin	Δ0.31	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 2.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 4,306 bp · p 0.32 · regional, not allelic
Overall
CADD	22.8	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

No allele count reported in gnomAD v4.1 (AN 1,341,522). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EN2
Protein: p.Gly111Val
Coding: c.332G>T
MANE Select: NM_001427
Type: single nucleotide variant
Location: chr7:155458709 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI 0.39 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.51
Residue 111: the 'disordered' region

Full EN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EN2 p.Asn68Ser Uncertain significance ★★ ⚠ same type
EN2 p.Leu318= Benign ★★ same type
EN2 p.Ser200= Benign ★★ same type
EN2 p.Ala109Val Uncertain significance ★ ⚠ same type
EN2 p.Ala167Ser Uncertain significance ★ ⚠ same type
EN2 p.Ala183Thr Uncertain significance ★ ⚠ same type
EN2 p.Ala297Thr Uncertain significance ★ ⚠ same type
EN2 p.Ala40Glu Uncertain significance ★ ⚠ same type

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/en2-p-gly111val (accessed [today's date]).

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