EXT1 p.Leu348=
c.1044G>A · rs1267068635 · VCV3060520
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
EXT1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.095 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 14.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,884 alleles
Overall
6.2e-05%
1/1,613,920 alleles · very rare
exomes 1/1,461,658 · genomes 0/152,262 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- EXT1
- Protein
- p.Leu348=
- Coding
- c.1044G>A
- MANE Select
- NM_000127
- dbSNP
- rs1267068635
- Type
- single nucleotide variant
- Location
- chr8:117837120 (GRCh38)
- Gene constraint
- LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.67 · 6 PDB
- Residue 348
- an α-helix
Disease context
EXT1-related disorder
Similar variants
- 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
- EXT1 p.Gln431Ter Pathogenic/Likely pathogenic ★★ same condition
- EXT1 p.Glu101Ter Likely pathogenic ★★ same condition
- EXT1 p.Glu604Ter 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-leu348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown