Is ELANE p.Val101fs (c.300dup) pathogenic?

ELANE p.Val101fs (c.300dup) is classified Uncertain significance in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-15). Absent from gnomAD; Associated with cyclic neutropenia.

What condition is associated with ELANE p.Val101fs (c.300dup)?

ELANE p.Val101fs (c.300dup) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Val101fs (c.300dup) in the general population?

ELANE p.Val101fs (c.300dup) 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.Val101fs

c.300dup · rs2145145158 · VCV1684713

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7	GERP -4.5

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.Val101fs
Coding: c.300dup
MANE Select: NM_001972
dbSNP: rs2145145158
Type: Duplication
Location: chr19:853335 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 101: a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (in scn1; located on the same allele as l-98; reduces proteolytic enzyme activity by slightly less than half; together with l-98 shows an additive effect with minimal remaining enzyme activity); a UniProt-annotated variant site (in scn1)

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

Also linked: neutropenia, severe congenital, 1, autosomal dominant

For Cyclic neutropenia (Orphanet):

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

Similar variants

ELANE p.Val101Met Pathogenic ★★ same residue
ELANE p.Val101Gly Pathogenic same residue
ELANE p.Val101= Benign/Likely benign ★★ same residue
ELANE p.Ala100_Val101insGlnValPheAla Pathogenic ★ same condition
ELANE p.Gly200fs Likely pathogenic ★ same condition
ELANE c.225-10_232dup Uncertain significance ★ same condition
ELANE c.367-10_367-9dup Conflicting classifications of pathogenicity ★ same condition
ELANE c.49_67+131dup Uncertain significance ★ 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-val101fs (accessed [today's date]).

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