Is ELANE p.Asn173= (c.519C>T) pathogenic?

ELANE p.Asn173= (c.519C>T) is classified Likely benign in ELANE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-10). Ultra-rare (popmax 0.017%, mid); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Asn173= (c.519C>T)?

ELANE p.Asn173= (c.519C>T) is associated with Inborn genetic diseases, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Asn173= (c.519C>T) in the general population?

ELANE p.Asn173= (c.519C>T) is ultra-rare (popmax 0.017%, mid) (gnomAD).

ELANE p.Asn173=

c.519C>T · rs200393776 · VCV513424

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.1	GERP -4.3
Overall
CADD	8.146	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,888 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00137% 22/1,609,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,888
African / African-American	0.0107%	9,366
Admixed American	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.00481%	20,809
South Asian	0.00439%	22,770
East Asian	0.00223%	44,884
European (non-Finnish)	8.47e-05%	1,179,942

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.Asn173=
Coding: c.519C>T
MANE Select: NM_001972
dbSNP: rs200393776
Type: single nucleotide variant
Location: chr19:855716 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 173: a disulfide bond; a β-strand; 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.Asn173Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ELANE p.Asn173Lys Benign ★ 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-asn173 (accessed [today's date]).

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