ENG p.Cys242Ter
c.726C>A · rs545465750 · VCV620110
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ENG-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.68, phastCons 0.61 |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- ENG
- Protein
- p.Cys242Ter
- Coding
- c.726C>A
- MANE Select
- NM_001114753
- dbSNP
- rs545465750
- Type
- single nucleotide variant
- Location
- chr9:127825321 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 242
- a disulfide bond; the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region
Disease context
ENG-related disorder
Similar variants
- ENG p.Cys242= Likely benign ★★ same residue
- ENG c.1686+1G>A Pathogenic ★★ same condition
- ENG c.-127C>T Pathogenic/Likely pathogenic ★★ same condition
- ENG p.Arg171Ter Pathogenic ★★ same condition
- ENG p.Gln508Ter Pathogenic ★★ same condition
- ENG p.Gln87Ter Pathogenic ★★ same condition
- ENG p.Gly501Ter Pathogenic/Likely pathogenic ★★ same condition
- ENG p.Tyr120Ter 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-cys242ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown