Is ELANE p.Ala57Asp (c.170C>A) pathogenic?

ELANE p.Ala57Asp (c.170C>A) is classified Pathogenic in ELANE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.9633); Very rare (popmax 8.53e-05%, nfe); Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Ala57Asp (c.170C>A)?

ELANE p.Ala57Asp (c.170C>A) is associated with neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Ala57Asp (c.170C>A) in the general population?

ELANE p.Ala57Asp (c.170C>A) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Ala57Asp (c.170C>A)?

AlphaMissense predicts likely pathogenic (score 0.9633) — an in-silico prediction, not a clinical call.

ELANE p.Ala57Asp

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.170C>A · VCV4076134

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.9633	likely pathogenic ✓ concordant with ClinVar · top 8% in ELANE
REVEL	0.611	indeterminate
SaProt	LLR -12.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.064	GERP -4.7
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	14.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,171,984 alleles

Overall 6.98e-05% 1/1,432,134 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.Ala57Asp
Coding: c.170C>A
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852978 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 57: a disulfide bond; 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

neutropenia, severe congenital, 1, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant severe congenital neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELANE p.Ala57Thr Pathogenic/Likely pathogenic ★★ same residue
ELANE p.Ala57= Benign/Likely benign ★★ same residue
ELANE p.Ala57Val Pathogenic/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.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-ala57asp (accessed [today's date]).

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