Is ELANE c.366+12C>A pathogenic?

ELANE c.366+12C>A is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-04). Ultra-rare (popmax 0.0531%, afr); Associated with neutropenia, severe congenital, 1, autosomal dominant.

How common is ELANE c.366+12C>A in the general population?

ELANE c.366+12C>A is ultra-rare (popmax 0.0531%, afr) (gnomAD).

ELANE c.366+12C>A

Q: What condition is associated with ELANE c.366+12C>A?

ELANE c.366+12C>A is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

rs377068029 · VCV1297446

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0531%, afr)

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP -2.5, phastCons 0.006
Overall
CADD	3.131	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0531% African / African-American · 39/73,428 alleles

Filtering AF 0.0399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0353%

Overall 0.00288% 45/1,562,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0531%	1,883
Remaining individualsnot grpmax-eligible	0.005%	19,986
Admixed American	0.00177%	56,472
South Asian	0.00114%	87,676
European (non-Finnish)	8.7e-05%	1,149,082

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ELANE
Coding: c.366+12C>A
MANE Select: NM_001972
dbSNP: rs377068029
Type: single nucleotide variant
Location: chr19:853415 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB

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 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
ELANE p.Ala57Thr Pathogenic/Likely pathogenic ★★ same condition
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg103Pro Pathogenic/Likely pathogenic ★★ same condition
ELANE p.Arg220Gln 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-c-366-plus-12c-a (accessed [today's date]).

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