Is ELANE p.Ala195fs (c.583del) pathogenic?

ELANE p.Ala195fs (c.583del) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-09). Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Ala195fs (c.583del)?

ELANE p.Ala195fs (c.583del) is associated with neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

ELANE p.Ala195fs

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.583del · VCV3255594

Likely pathogenic Single submitter

Classification

Likely pathogenic

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (4 of 5, 15 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -4.2

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

Variant & gene context

Gene: ELANE
Protein: p.Ala195fs
Coding: c.583del
MANE Select: NM_001972
Type: Deletion
Location: chr19:855779 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 195: a disulfide bond; the peptidase s1 domain; a UniProt-annotated variant site (in scn1 and ch)

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

For Autosomal dominant severe congenital neutropenia (Orphanet):

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

Similar variants

ELANE p.Ala195Asp Uncertain significance ★★ ⚠ same residue
ELANE p.Ala195= Likely benign ★★ same residue
ELANE p.Ala195Thr Uncertain significance ★ ⚠ same residue
ELANE p.Pro111_Val112insTer Uncertain significance ★★ same condition
ELANE c.597+5del Pathogenic ★ same condition
ELANE p.Asp201fs Likely pathogenic ★ same condition
ELANE p.Asp230fs Pathogenic ★ same condition
ELANE p.Gly192fs 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-ala195fs (accessed [today's date]).

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