Is ELANE p.Ser244fs (c.731_732del) pathogenic?

ELANE p.Ser244fs (c.731732del) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). Absent from gnomAD; Associated with cyclic neutropenia.

What condition is associated with ELANE p.Ser244fs (c.731_732del)?

ELANE p.Ser244fs (c.731_732del) is associated with cyclic neutropenia (ClinVar).

How common is ELANE p.Ser244fs (c.731_732del) in the general population?

ELANE p.Ser244fs (c.731_732del) is absent from gnomAD (gnomAD).

How is Cyclic neutropenia inherited?

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

ELANE p.Ser244fs

c.731_732del · rs2512169449 · VCV2431429

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cyclic neutropenia

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 in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 2.1, phastCons 0.056

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELANE
Protein: p.Ser244fs
Coding: c.731_732del
MANE Select: NM_001972
dbSNP: rs2512169449
Type: Microsatellite
Location: chr19:856089 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 244: an α-helix; the peptidase s1 domain

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

Disease context

cyclic neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cyclic neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ELANE p.Arg6dup Uncertain significance ★★ same condition
ELANE p.Cys9fs Uncertain significance ★ same condition
ELANE p.Ser244Phe Uncertain significance ★ ⚠ same residue
ELANE p.Thr128del Uncertain significance ★ same condition
ELANE c.366+17_366+21del Likely benign ★ same condition
ELANE c.597+1G>A Pathogenic ★★ same condition
ELANE c.597+1G>C Pathogenic ★★ same condition
ELANE c.597+1G>T 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-ser244fs (accessed [today's date]).

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