Is ELANE p.Val190fs (c.566dup) pathogenic?

ELANE p.Val190fs (c.566dup) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Absent from gnomAD; Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Val190fs (c.566dup)?

ELANE p.Val190fs (c.566dup) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

How common is ELANE p.Val190fs (c.566dup) in the general population?

ELANE p.Val190fs (c.566dup) is absent from gnomAD (gnomAD).

ELANE p.Val190fs

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.566dup · rs2512168637 · VCV2921938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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, 32 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 -0.28	GERP -4.2

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.Val190fs
Coding: c.566dup
MANE Select: NM_001972
dbSNP: rs2512168637
Type: Duplication
Location: chr19:855762 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 190: 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

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.Val190= Likely pathogenic ★★ same residue
ELANE p.Val190Gly Uncertain significance ★★ ⚠ same residue
ELANE p.Val190Leu Uncertain significance ★ ⚠ same residue
ELANE p.Val190Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ELANE p.Val101fs Uncertain significance ★★ same condition
ELANE p.Ala100_Val101insGlnValPheAla Pathogenic ★ same condition
ELANE p.Gly200fs Likely pathogenic ★ same condition
ELANE c.225-10_232dup 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-val190fs (accessed [today's date]).

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