Is ELANE p.Leu121= (c.363C>G) pathogenic?

ELANE p.Leu121= (c.363C>G) is classified Likely benign in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-15). Very rare (popmax 0.00507%, amr); Associated with cyclic neutropenia.

What condition is associated with ELANE p.Leu121= (c.363C>G)?

ELANE p.Leu121= (c.363C>G) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Leu121= (c.363C>G) in the general population?

ELANE p.Leu121= (c.363C>G) is very rare (popmax 0.00507%, amr) (gnomAD).

How is Cyclic neutropenia inherited?

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

ELANE p.Leu121=

c.363C>G · rs765488502 · VCV741308

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00507%, amr)

Conditions

cyclic neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3
Overall
CADD	3.708	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00507% Admixed American · 3/59,196 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000673%

Overall 0.000207% 3/1,452,224 alleles · very rare

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
Protein: p.Leu121=
Coding: c.363C>G
MANE Select: NM_001972
dbSNP: rs765488502
Type: single nucleotide variant
Location: chr19:853400 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 121: a β-strand; the peptidase s1 domain; 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.Leu121Arg Likely pathogenic ★ same residue
ELANE p.Leu121Pro Uncertain significance ★ ⚠ same residue
ELANE p.Leu121Ile 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
ELANE p.Ala57Thr 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-leu121 (accessed [today's date]).

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