EXTL3 p.Ile768=
c.2304C>T · rs190213591 · VCV1578264
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.423 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -3.6 |
| Overall | ||
| CADD | 5.698 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,058 alleles
Filtering AF
0.0114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0107%
Overall
0.011%
178/1,614,014 alleles · ultra-rare
exomes 154/1,461,680 · genomes 24/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,029 |
| Admixed American | 0.0133% | 7,502 |
| European (non-Finnish) | 0.0131% | 7,612 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
| African / African-American | 0.008% | 12,507 |
| East Asian | 0.00223% | 44,888 |
| South Asian | 0.0011% | 91,078 |
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.Ile768=
- Coding
- c.2304C>T
- MANE Select
- NM_001440
- dbSNP
- rs190213591
- Type
- single nucleotide variant
- Location
- chr8:28737546 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
Similar variants
- EXTL3 p.Ile768Thr Uncertain significance ★ ⚠ same residue
- 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
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-ile768 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown