Is ELANE p.Cys223= (c.669C>T) pathogenic?

ELANE p.Cys223= (c.669C>T) is classified Likely benign in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-03). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Cys223= (c.669C>T)?

ELANE p.Cys223= (c.669C>T) is associated with Inborn genetic diseases, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Cys223= (c.669C>T) in the general population?

ELANE p.Cys223= (c.669C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

ELANE p.Cys223=

c.669C>T · VCV4618392

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

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 -12	GERP -4.5
Overall
CADD	0.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,090 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000434% 7/1,613,434 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,545
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,938
European (non-Finnish)	0.000169%	590,023

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.Cys223=
Coding: c.669C>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:856029 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 223: a disulfide bond; the peptidase s1 domain

Full ELANE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

ELANE p.Cys223Ter Pathogenic ★★ same residue
ELANE p.Cys223fs Likely pathogenic 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
ELANE p.Ala61Val 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-cys223 (accessed [today's date]).

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