Is ELANE p.Arg34Trp (c.100C>T) pathogenic?

ELANE p.Arg34Trp (c.100C>T) is classified Likely benign in ELANE (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-30). AlphaMissense: likely benign (0.3344); Ultra-rare (popmax 0.0268%, eas); Associated with cyclic neutropenia.

What condition is associated with ELANE p.Arg34Trp (c.100C>T)?

ELANE p.Arg34Trp (c.100C>T) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Arg34Trp (c.100C>T) in the general population?

ELANE p.Arg34Trp (c.100C>T) is ultra-rare (popmax 0.0268%, eas) (gnomAD).

How is Cyclic neutropenia inherited?

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

What do computational predictors say about ELANE p.Arg34Trp (c.100C>T)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

ELANE p.Arg34Trp

c.100C>T · rs201163886 · VCV1136280

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cyclic neutropenia

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3	GERP 0.049, phastCons 0.051
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	25.5	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 0.0268% East Asian · 12/44,732 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00113% 18/1,596,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0268%	3,728
African / African-American	0.00401%	24,932
Remaining individualsnot grpmax-eligible	0.00322%	31,010
European (non-Finnish)	8.49e-05%	1,177,238

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_001972
dbSNP: rs201163886
Type: single nucleotide variant
Location: chr19:852908 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 34: 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.Arg34= Likely benign ★★ same residue
ELANE p.Arg34Leu 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-arg34trp (accessed [today's date]).

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