ESPN p.Leu366del
c.1096_1098del · rs774970657 · VCV1403406
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00593%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 0.018, phastCons 0.88 |
| Overall | ||
| CADD | 8.645 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00593%
European (non-Finnish) · 70/1,180,020 alleles
Filtering AF
0.00478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00439%
Overall
0.00452%
73/1,614,182 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00593% | 16,857 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| African / African-American | 0.00133% | 75,050 |
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
- ESPN
- Protein
- p.Leu366del
- Coding
- c.1096_1098del
- MANE Select
- NM_031475
- dbSNP
- rs774970657
- Type
- Deletion
- Location
- chr1:6444585 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 366
- the 'disordered' region
Similar variants
- ESPN p.Arg632_Ser633delinsPro Uncertain significance ★★ same type
- ESPN c.1464+19del Benign/Likely benign ★★ same type
- ESPN p.Pro602_Pro605del Benign/Likely benign ★★ same type
- ESPN c.487_488+2del Likely pathogenic ★ same type
- ESPN p.Arg550fs Pathogenic ★ same type
- ESPN p.Arg790_Arg795del Pathogenic ★ same type
- ESPN p.Gln713fs Likely pathogenic ★ same type
- ESPN p.Glu608fs Likely pathogenic ★ 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/espn-p-leu366del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown