Is ELANE p.Arg81Pro (c.242G>C) pathogenic?

ELANE p.Arg81Pro (c.242G>C) is classified Pathogenic/Likely pathogenic in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-26). AlphaMissense: likely pathogenic (0.8187); Absent from gnomAD v4.1; Associated with cyclic neutropenia.

What condition is associated with ELANE p.Arg81Pro (c.242G>C)?

ELANE p.Arg81Pro (c.242G>C) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Arg81Pro (c.242G>C) in the general population?

ELANE p.Arg81Pro (c.242G>C) is absent from gnomAD v4.1 (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.Arg81Pro (c.242G>C)?

AlphaMissense predicts likely pathogenic (score 0.8187) — an in-silico prediction, not a clinical call.

ELANE p.Arg81Pro

c.242G>C · rs762470485 · VCV1343817

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8187 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cyclic neutropenia

Computational evidence

Protein change
AlphaMissense	0.8187	likely pathogenic ✓ concordant with ClinVar
REVEL	0.545	indeterminate
SaProt	LLR -14.17	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 0.067	GERP -3.1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	14.95	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELANE
Protein: p.Arg81Pro
Coding: c.242G>C
MANE Select: NM_001972
dbSNP: rs762470485
Type: single nucleotide variant
Location: chr19:853279 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 81: a β-strand; 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

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.Arg81= Likely benign ★★ same residue
ELANE p.Arg81Gln Uncertain significance ★ ⚠ same residue
ELANE p.Arg81Leu Uncertain significance ★ ⚠ same residue
ELANE p.Arg81Trp 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

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-arg81pro (accessed [today's date]).

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