EXT1 p.Glu413Ter
c.1237G>T · VCV4901503
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
EXT1-related disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 11 |
| Splicing | ||
| SpliceAI | Δ0.56 | donor loss, 47 bp away · masked 0 · deltas |
| Pangolin | Δ0.32 | loss · gain 0.08 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 46.0 | 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
- EXT1
- Protein
- p.Glu413Ter
- Coding
- c.1237G>T
- MANE Select
- NM_000127
- Type
- single nucleotide variant
- Location
- chr8:117830277 (GRCh38)
- Gene constraint
- LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.67 · 6 PDB
- Residue 413
- an α-helix
Disease context
EXT1-related disorders
Similar variants
- EXT1 p.Glu413Asp Uncertain significance ★★ ⚠ same residue
- EXT1 p.Glu413Lys Uncertain significance ★ ⚠ same residue
- EXT1 p.Glu413= Likely benign ★ same residue
- EXT1 c.1633-2A>G Pathogenic ★★ same condition
- EXT1 c.1722+1G>A Pathogenic ★★ same condition
- EXT1 c.1723-1G>C Pathogenic ★★ same condition
- EXT1 c.962+1G>T Pathogenic ★★ same condition
- EXT1 p.Arg86Ter Pathogenic/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/ext1-p-glu413ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown