ELANE c.224+99del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 36.1%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +99 | deep intronic (+99 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -1.6, phastCons 0.001 |
| Overall | ||
| CADD | 1.281 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | G-rich low complexity · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.1%
Middle Eastern · 1,053/2,918 alleles
Filtering AF
34.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 33.5%
Overall
25.7%
238,388/928,852 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 36.1% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 31.9% | 3 |
| European (non-Finnish) | 27.1% | 4 |
| Remaining individualsnot grpmax-eligible | 26.8% | 4 |
| African / African-American | 26.7% | 4 |
| Amishnot grpmax-eligible | 23.8% | 4 |
| South Asian | 20.7% | 5 |
| Admixed American | 17.4% | 6 |
| Finnishnot grpmax-eligible | 16.6% | 6 |
| East Asian | 4.26% | 23 |
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
- ELANE
- Coding
- c.224+99del
- MANE Select
- NM_001972
- dbSNP
- rs34535016
- Type
- Deletion
- Location
- chr19:853123 (GRCh38)
- Gene constraint
- LOEUF 1.245 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.42 · 38 PDB
Similar variants
- ELANE p.Pro111_Val112insTer Uncertain significance ★★ same type
- ELANE c.597+5del Pathogenic ★ same type
- ELANE p.Ala195fs Likely pathogenic ★ same type
- ELANE p.Ala236fs Likely pathogenic ★ same type
- ELANE p.Arg182fs Pathogenic ★ same type
- ELANE p.Asn113_Ile120del Pathogenic ★ same type
- ELANE p.Asp201fs Likely pathogenic ★ same type
- ELANE p.Asp230fs 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/elane-c-224-plus-99del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown