EXTL3 p.Val38=
c.114C>T · rs985736527 · VCV1981927
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00508%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
European (non-Finnish) · 60/1,180,050 alleles
Filtering AF
0.00402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00362%
Overall
0.00384%
62/1,614,192 alleles · very rare
exomes 62/1,461,862 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00508% | 19,668 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
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.Val38=
- Coding
- c.114C>T
- MANE Select
- NM_001440
- dbSNP
- rs985736527
- Type
- single nucleotide variant
- Location
- chr8:28716173 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 38
- the 'required for interaction with reg3a' region
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-val38 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown