Is ELANE p.Pro42= (c.126C>T) pathogenic?

ELANE p.Pro42= (c.126C>T) is classified Benign/Likely benign in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00297%, nfe); Associated with cyclic neutropenia.

What condition is associated with ELANE p.Pro42= (c.126C>T)?

ELANE p.Pro42= (c.126C>T) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Pro42= (c.126C>T) in the general population?

ELANE p.Pro42= (c.126C>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

How is Cyclic neutropenia inherited?

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

ELANE p.Pro42=

c.126C>T · rs587780933 · VCV137198

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Conditions

cyclic neutropenia

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 Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -4, phastCons 0.001
Overall
CADD	13.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,177,990 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00256% 37/1,445,368 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,055
European (non-Finnish)grpmax	0.00297%	33,657

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro42=
Coding: c.126C>T
MANE Select: NM_001972
dbSNP: rs587780933
Type: single nucleotide variant
Location: chr19:852934 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 42: a UniProt-annotated variant site (in scn1); the peptidase s1 domain

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

Disease context

cyclic neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Cyclic neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ELANE p.Pro42Ser Uncertain significance ★★ ⚠ same residue
ELANE p.Pro42fs 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
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-pro42 (accessed [today's date]).

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