EXTL3 p.Arg513=
c.1539C>T · rs141360609 · VCV2166201
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0387%, 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 1.3 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 8.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0387%
African / African-American · 29/74,946 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0239%
Overall
0.00229%
37/1,614,126 alleles · ultra-rare
exomes 20/1,461,882 · genomes 17/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0387% | 2,584 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| South Asian | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000169% | 590,030 |
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.Arg513=
- Coding
- c.1539C>T
- MANE Select
- NM_001440
- dbSNP
- rs141360609
- Type
- single nucleotide variant
- Location
- chr8:28717598 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 513
- a UniProt-annotated variant site (in isdna; changed glycosaminoglycan synthesis; no localization to golgi apparatus in patient fibroblasts); an α-helix
Similar variants
- EXTL3 p.Arg513Gly Uncertain significance ★★ ⚠ same residue
- EXTL3 p.Arg513Cys Uncertain significance ★ ⚠ same residue
- EXTL3 p.Arg513His 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
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-arg513 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown