Is ELANE p.Leu84Pro (c.251T>C) pathogenic?

ELANE p.Leu84Pro (c.251T>C) is classified Pathogenic/Likely pathogenic in ELANE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-07). AlphaMissense: likely pathogenic (0.9617); Absent from gnomAD v4.1; Associated with ELANE-related disorder.

What condition is associated with ELANE p.Leu84Pro (c.251T>C)?

ELANE p.Leu84Pro (c.251T>C) is associated with ELANE-related disorder, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Leu84Pro (c.251T>C) in the general population?

ELANE p.Leu84Pro (c.251T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Leu84Pro (c.251T>C)?

AlphaMissense predicts likely pathogenic (score 0.9617) — an in-silico prediction, not a clinical call.

ELANE p.Leu84Pro

c.251T>C · rs1064793108 · VCV418179

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9617 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ELANE-related disorder

Computational evidence

Protein change
AlphaMissense	0.9617	likely pathogenic ✓ concordant with ClinVar · top 8% in ELANE
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -14.89	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 7.6	GERP 2.2, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	23.7	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.Leu84Pro
Coding: c.251T>C
MANE Select: NM_001972
dbSNP: rs1064793108
Type: single nucleotide variant
Location: chr19:853288 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 84: 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

ELANE-related disorder

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

Similar variants

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
ELANE p.Arg103Leu Likely pathogenic ★★ same condition
ELANE p.Arg103Pro 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-leu84pro (accessed [today's date]).

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