Is ELANE p.Cys55Arg (c.163T>C) pathogenic?

ELANE p.Cys55Arg (c.163T>C) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-12). AlphaMissense: likely pathogenic (0.9734); Absent from gnomAD v4.1; Associated with cyclic neutropenia.

What condition is associated with ELANE p.Cys55Arg (c.163T>C)?

ELANE p.Cys55Arg (c.163T>C) is associated with cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Cys55Arg (c.163T>C) in the general population?

ELANE p.Cys55Arg (c.163T>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.Cys55Arg (c.163T>C)?

AlphaMissense predicts likely pathogenic (score 0.9734) — an in-silico prediction, not a clinical call.

ELANE p.Cys55Arg

c.163T>C · rs2512164548 · VCV2156128

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9734 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,216)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cyclic neutropenia

Computational evidence

Protein change
AlphaMissense	0.9734	likely pathogenic ✓ concordant with ClinVar · top 6% in ELANE
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -15.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,587,216). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELANE
Protein: p.Cys55Arg
Coding: c.163T>C
MANE Select: NM_001972
dbSNP: rs2512164548
Type: single nucleotide variant
Location: chr19:852971 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 55: a disulfide bond; a β-strand; 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.Cys55= Likely benign ★★ same residue
ELANE p.Cys55Tyr Pathogenic ★ same residue
ELANE p.Cys55Ter Uncertain significance ★ same residue
ELANE p.Cys55del Uncertain significance ★ same residue
ELANE p.Cys55Ser 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

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-cys55arg (accessed [today's date]).

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