ELANE p.Leu206Ser
c.617T>C · VCV4939519
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.989 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
ELANE-related disorders
Computational evidence
| Protein change | ||
| AlphaMissense | 0.989 | likely pathogenic ✓ concordant with ClinVar · top 2% in ELANE |
|---|---|---|
| REVEL | 0.854 | moderately pathogenic-leaning |
| SaProt | LLR -17.68 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 2.4, phastCons 1 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic |
| Overall | ||
| CADD | 25.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ELANE
- Protein
- p.Leu206Ser
- Coding
- c.617T>C
- MANE Select
- NM_001972
- Type
- single nucleotide variant
- Location
- chr19:855977 (GRCh38)
- Gene constraint
- LOEUF 1.245 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.42 · 38 PDB
- Residue 206
- a disulfide bond; a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (in ch); a UniProt-annotated variant site (in scn1)
Disease context
ELANE-related disorders
Similar variants
- ELANE p.Leu206Phe Likely pathogenic ★ same residue
- ELANE p.Leu206= Likely benign ★ same residue
- ELANE c.597+1G>T Pathogenic ★★ same condition
- ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ same condition
- ELANE p.Arg103Leu Likely pathogenic ★★ same condition
- ELANE p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ELANE p.Gly214Arg Pathogenic ★★ same condition
- ELANE p.Leu84Pro 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-leu206ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown