ELANE p.Ala140=
c.420T>A · VCV4017363
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Conditions
3
Inborn genetic diseases
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 -1.1 | GERP -4.3 |
| Overall | ||
| CADD | 1.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,820 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000276%
4/1,450,776 alleles · very rare
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
- Protein
- p.Ala140=
- Coding
- c.420T>A
- MANE Select
- NM_001972
- Type
- single nucleotide variant
- Location
- chr19:855617 (GRCh38)
- Gene constraint
- LOEUF 1.245 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.42 · 38 PDB
- Residue 140
- the peptidase s1 domain
Similar variants
- ELANE p.Ala140Thr Uncertain significance ★★ ⚠ same residue
- ELANE p.Ala140Val Uncertain significance ★★ ⚠ same residue
- ELANE p.Ala140Ser Uncertain significance ⚠ same residue
- ELANE c.597+1G>A Pathogenic ★★ same condition
- ELANE c.597+1G>C Pathogenic ★★ same condition
- ELANE c.597+1G>T Pathogenic ★★ same condition
- ELANE c.597+5G>A Pathogenic/Likely pathogenic ★★ same condition
- ELANE p.Ala57Thr Pathogenic/Likely pathogenic ★★ same condition
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-p-ala140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown