EXT2 p.Leu37Phe
c.109C>T · VCV4882653
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5536 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5536 | ambiguous |
|---|---|---|
| REVEL | 0.21 | benign-leaning |
| SaProt | LLR -7.12 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 99 kb · p 0.085 · regional, not allelic |
| Overall | ||
| CADD | 21.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- EXT2
- Protein
- p.Leu37Phe
- Coding
- c.109C>T
- MANE Select
- NM_207122
- Type
- single nucleotide variant
- Location
- chr11:44107821 (GRCh38)
- Gene constraint
- LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59 · 6 PDB
Similar variants
- EXT2 p.Leu37= Likely benign ★ same residue
- EXT2 c.1079+1G>A Pathogenic ★★ same type
- EXT2 c.1079+1G>T Pathogenic ★★ same type
- EXT2 c.1173+1G>A Pathogenic ★★ same type
- EXT2 c.1662+1G>C Likely pathogenic ★★ same type
- EXT2 c.536+1G>A Pathogenic ★★ same type
- EXT2 c.626+1G>A Pathogenic ★★ same type
- EXT2 c.626+1G>C 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/ext2-p-leu37phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown