Is ELANE p.Val190= (c.570G>A) pathogenic?

ELANE p.Val190= (c.570G>A) is classified Likely pathogenic in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-01). Absent from gnomAD v4.1; Associated with cyclic neutropenia.

What condition is associated with ELANE p.Val190= (c.570G>A)?

ELANE p.Val190= (c.570G>A) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Val190= (c.570G>A) in the general population?

ELANE p.Val190= (c.570G>A) is absent from gnomAD v4.1 (gnomAD).

How is Cyclic neutropenia inherited?

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

ELANE p.Val190=

c.570G>A · rs2512168653 · VCV2925634

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cyclic neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.49	donor gain · deltas
Pangolin	Δ0.49	gain · loss 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.61	GERP -1.6, phastCons 0.055
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELANE
Protein: p.Val190=
Coding: c.570G>A
MANE Select: NM_001972
dbSNP: rs2512168653
Type: single nucleotide variant
Location: chr19:855767 (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

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.Val190Gly Uncertain significance ★★ ⚠ same residue
ELANE p.Val190Leu Uncertain significance ★ ⚠ same residue
ELANE p.Val190Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ELANE p.Val190fs Uncertain significance ★ same residue
ELANE c.597+1G>A Pathogenic ★★ same condition
ELANE c.597+1G>C Pathogenic ★★ same condition
ELANE c.597+1G>T Pathogenic ★★ same condition
ELANE c.597+5G>A Pathogenic/Likely 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-val190 (accessed [today's date]).

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