EXTL3 p.Val692=
c.2076C>T · rs776600684 · VCV2181024
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00975%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.057 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -3.9 |
| Overall | ||
| CADD | 0.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00975%
European (non-Finnish) · 115/1,180,026 alleles
Filtering AF
0.00826%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00774%
Overall
0.00744%
120/1,613,988 alleles · very rare
exomes 116/1,461,884 · genomes 4/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00975% | 10,261 |
| Admixed American | 0.00333% | 29,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| African / African-American | 0.00134% | 74,876 |
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.Val692=
- Coding
- c.2076C>T
- MANE Select
- NM_001440
- dbSNP
- rs776600684
- Type
- single nucleotide variant
- Location
- chr8:28718135 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 692
- a β-strand
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-val692 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown