EXTL3 p.Phe430=
c.1290C>T · rs199880183 · VCV741027
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -4.7 | GERP -3.6 |
| Overall | ||
| CADD | 3.582 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00477%
77/1,614,184 alleles · ultra-rare
exomes 68/1,461,884 · genomes 9/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| African / African-American | 0.0133% | 7,505 |
| Finnishnot grpmax-eligible | 0.00937% | 10,673 |
| South Asian | 0.00769% | 13,011 |
| East Asian | 0.00446% | 22,433 |
| European (non-Finnish) | 0.00415% | 24,082 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
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.Phe430=
- Coding
- c.1290C>T
- MANE Select
- NM_001440
- dbSNP
- rs199880183
- Type
- single nucleotide variant
- Location
- chr8:28717349 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 430
- 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-phe430 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown