EXTL3 p.Ile780=
c.2340C>T · rs148404093 · VCV728869
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0675%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.265 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.54 | GERP -0.17, phastCons 1 |
| Overall | ||
| CADD | 7.488 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0675%
European (non-Finnish) · 797/1,179,886 alleles
Filtering AF
0.0636%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.062%
Overall
0.0521%
841/1,614,032 alleles · ultra-rare
exomes 797/1,461,688 · genomes 44/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0675% | 1,480 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| Admixed American | 0.0167% | 6,001 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.0133% | 7,505 |
| Finnishnot grpmax-eligible | 0.00156% | 64,048 |
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.Ile780=
- Coding
- c.2340C>T
- MANE Select
- NM_001440
- dbSNP
- rs148404093
- Type
- single nucleotide variant
- Location
- chr8:28737582 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 780
- a turn
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-ile780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown