Is ELANE p.Ala195= (c.585C>T) pathogenic?

ELANE p.Ala195= (c.585C>T) is classified Likely benign in ELANE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0187%, afr); Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Ala195= (c.585C>T)?

ELANE p.Ala195= (c.585C>T) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

How common is ELANE p.Ala195= (c.585C>T) in the general population?

ELANE p.Ala195= (c.585C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

ELANE p.Ala195=

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.585C>T · rs777834651 · VCV1604951

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

neutropenia, severe congenital, 1, autosomal dominant

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 -14	GERP -4.2
Overall
CADD	0.408	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,888 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00124% 20/1,608,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,349
South Asian	0.0033%	30,341
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,308
European (non-Finnish)	8.47e-05%	1,179,949

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.Ala195=
Coding: c.585C>T
MANE Select: NM_001972
dbSNP: rs777834651
Type: single nucleotide variant
Location: chr19:855782 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 195: a disulfide bond; the peptidase s1 domain; a UniProt-annotated variant site (in scn1 and ch)

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

Also linked: cyclic neutropenia

For Autosomal dominant severe congenital neutropenia (Orphanet):

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

Similar variants

ELANE p.Ala195Asp Uncertain significance ★★ ⚠ same residue
ELANE p.Ala195Thr Uncertain significance ★ ⚠ same residue
ELANE p.Ala195fs Likely pathogenic ★ same residue
ELANE p.Ala195Gly Uncertain significance ★ ⚠ same residue
ELANE p.Ala195Pro 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

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-ala195 (accessed [today's date]).

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