Is ELANE p.Arg103His (c.308G>A) pathogenic?

ELANE p.Arg103His (c.308G>A) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.1375); Absent from gnomAD v4.1; Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Arg103His (c.308G>A)?

ELANE p.Arg103His (c.308G>A) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

How common is ELANE p.Arg103His (c.308G>A) in the general population?

ELANE p.Arg103His (c.308G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Arg103His (c.308G>A)?

AlphaMissense predicts likely benign (score 0.1375) — an in-silico prediction, not a clinical call.

ELANE p.Arg103His

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.308G>A · VCV3762106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1375 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,326)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.1375	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1, phastCons 0.001
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 1,611,326). 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.Arg103His
Coding: c.308G>A
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:853345 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 103: a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (in scn1)

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.Arg103Pro Pathogenic/Likely pathogenic ★★ same residue
ELANE p.Arg103Leu Likely pathogenic ★★ ⚠ same residue
ELANE p.Arg103= Likely benign ★ 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

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-arg103his (accessed [today's date]).

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