EXT1 p.Ala689fs
c.2065del · VCV4713230
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
hereditary multiple osteochondromas
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 | escapes | premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- EXT1
- Protein
- p.Ala689fs
- Coding
- c.2065del
- MANE Select
- NM_000127
- Type
- Deletion
- Location
- chr8:117799888 (GRCh38)
- Gene constraint
- LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.67 · 6 PDB
Disease context
hereditary multiple osteochondromas — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Multiple osteochondromas (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood
- Prevalence
- >1 / 1000 (Specific population)
Similar variants
- EXT1 p.Ala689Thr Uncertain significance ★★ ⚠ same residue
- EXT1 p.Ala689Ser Uncertain significance ★ ⚠ same residue
- EXT1 p.Ala689= Likely benign ★ same residue
- EXT1 p.Ala594fs Pathogenic/Likely pathogenic ★★ same condition
- EXT1 p.Arg405fs Pathogenic ★★ same condition
- EXT1 p.Gln508fs Pathogenic ★★ same condition
- EXT1 p.Glu39fs Pathogenic ★★ same condition
- EXT1 p.Leu490fs 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-ala689fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown