ENG p.Gln33Ter
c.97C>T · rs1564462827 · VCV618086
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 2 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 37.0 | 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.Gln33Ter
- Coding
- c.97C>T
- MANE Select
- NM_001114753
- dbSNP
- rs1564462827
- Type
- single nucleotide variant
- Location
- chr9:127843216 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 33
- a disulfide bond; the 'required for interaction with gdf2' region; the 'or1, n-terminal part' region
Similar variants
- ENG p.Gln33Pro Uncertain significance ★ ⚠ same residue
- ENG p.Gln33fs Pathogenic ★★ same residue
- ENG p.Arg529His Pathogenic ★★★ same type
- ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same type
- ENG p.Cys382Tyr Pathogenic ★★★ same type
- ENG p.Cys549Gly Likely pathogenic ★★★ same type
- ENG p.Gly331Ser Pathogenic ★★★ ⚠ same type
- ENG p.Gly603Arg Likely pathogenic ★★★ 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/eng-p-gln33ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown