Is ELANE p.Cys9fs (c.26_27del) pathogenic?

ELANE p.Cys9fs (c.2627del) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Cys9fs (c.26_27del)?

ELANE p.Cys9fs (c.26_27del) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

ELANE p.Cys9fs

Q: How is Autosomal dominant severe congenital neutropenia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.26_27del · VCV4785032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.33	GERP -1.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ELANE
Protein: p.Cys9fs
Coding: c.26_27del
MANE Select: NM_001972
Type: Microsatellite
Location: chr19:852352 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB

Full ELANE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neutropenia, severe congenital, 1, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cyclic neutropenia

For Autosomal dominant severe congenital neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELANE p.Cys9Arg Uncertain significance ★ ⚠ same residue
ELANE p.Arg6dup Uncertain significance ★★ same condition
ELANE p.Ser244fs Likely pathogenic ★ same condition
ELANE p.Cys9Trp Uncertain significance ★ ⚠ same residue
ELANE p.Thr128del Uncertain significance ★ same condition
ELANE c.366+17_366+21del Likely benign ★ same condition
ELANE p.Cys9= Likely benign ★ same residue
ELANE c.597+1G>A 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-cys9fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown