EXTL3 p.Pro702=
c.2106A>G · rs1490072293 · VCV1572678
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.037 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.1 | GERP -3.9 |
| Overall | ||
| CADD | 0.346 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,074 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,176 alleles · very rare
exomes 3/1,461,876 · genomes 0/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Pro702=
- Coding
- c.2106A>G
- MANE Select
- NM_001440
- dbSNP
- rs1490072293
- Type
- single nucleotide variant
- Location
- chr8:28718165 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 702
- an α-helix
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-pro702 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown