Is ELANE p.Thr58= (c.174C>T) pathogenic?

ELANE p.Thr58= (c.174C>T) is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-28). Ultra-rare (popmax 0.0213%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with ELANE p.Thr58= (c.174C>T)?

ELANE p.Thr58= (c.174C>T) is associated with autoinflammatory syndrome, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Thr58= (c.174C>T) in the general population?

ELANE p.Thr58= (c.174C>T) is ultra-rare (popmax 0.0213%, nfe) (gnomAD).

ELANE p.Thr58=

c.174C>T · rs199714513 · VCV467830

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, nfe)

Conditions

autoinflammatory syndrome

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 -5.8	GERP -4.7
Overall
CADD	1.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% European (non-Finnish) · 250/1,171,010 alleles

Filtering AF 0.0192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.0178% 282/1,582,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0213%	4,684
Admixed American	0.0192%	5,201
Remaining individualsnot grpmax-eligible	0.0179%	5,598
Middle Eastern	0.0167%	5,974
Finnishnot grpmax-eligible	0.0101%	9,912
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,198
African / African-American	0.00268%	37,246
South Asian	0.00113%	88,470

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.Thr58=
Coding: c.174C>T
MANE Select: NM_001972
dbSNP: rs199714513
Type: single nucleotide variant
Location: chr19:852982 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 58: 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

autoinflammatory syndrome — 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.Thr58Ile Uncertain significance ★★ ⚠ same residue
ELANE p.Thr58Pro Uncertain significance ★ ⚠ same residue
ELANE p.Thr58Ser 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-thr58 (accessed [today's date]).

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