Is ENG p.Ser123fs (c.366del) pathogenic?

ENG p.Ser123fs (c.366del) is classified Likely pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-25). Associated with ENG-related disorder.

What condition is associated with ENG p.Ser123fs (c.366del)?

ENG p.Ser123fs (c.366del) is associated with ENG-related disorder (ClinVar).

ENG p.Ser123fs

c.366del · VCV4904635

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ENG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.47	GERP -1.5, phastCons 0.013

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ENG
Protein: p.Ser123fs
Coding: c.366del
MANE Select: NM_001114753
Type: Deletion
Location: chr9:127826667 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 123: a turn; a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region

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

Disease context

ENG-related disorder

Similar variants

ENG c.1687delG Pathogenic ★★ same condition
ENG p.Asn423fs Pathogenic ★★ same condition
ENG c.1311+4_1311+8del Likely pathogenic ★ same condition
ENG c.668_689+6del Likely pathogenic ★ same condition
ENG p.Gly509fs Likely pathogenic ★ same condition
ENG p.Leu495fs Likely pathogenic ★ same condition
ENG p.Pro392_Ser393insTer Likely pathogenic ★ same condition
ENG p.Pro555fs 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/eng-p-ser123fs (accessed [today's date]).

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