EXTL3 p.Ile46=
c.138C>T · rs141531460 · VCV1595325
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.108%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -3.4 |
| Overall | ||
| CADD | 4.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.108%
African / African-American · 81/75,034 alleles
Filtering AF
0.0889%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.082%
Overall
0.00688%
111/1,614,172 alleles · rare
exomes 58/1,461,868 · genomes 53/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.108% | 926 |
| Admixed American | 0.0167% | 6,003 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| East Asian | 0.00223% | 44,882 |
| European (non-Finnish) | 0.00127% | 78,670 |
| South Asian | 0.0011% | 91,084 |
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
- EXTL3
- Protein
- p.Ile46=
- Coding
- c.138C>T
- MANE Select
- NM_001440
- dbSNP
- rs141531460
- Type
- single nucleotide variant
- Location
- chr8:28716197 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 46
- the 'required for interaction with reg3a' region
Similar variants
- EXTL3 p.Pro318Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- EXTL3 p.Ala373Thr Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala385Val Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala481Val Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala482Thr Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala507Ser Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala560Ser Uncertain significance ★★ ⚠ same type
- EXTL3 p.Ala585Thr Uncertain significance ★★ ⚠ 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/extl3-p-ile46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown