Is ELANE p.Pro42Ser (c.124C>T) pathogenic?

ELANE p.Pro42Ser (c.124C>T) is classified Uncertain significance in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.7517); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Pro42Ser (c.124C>T)?

ELANE p.Pro42Ser (c.124C>T) is associated with Inborn genetic diseases, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Pro42Ser (c.124C>T) in the general population?

ELANE p.Pro42Ser (c.124C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely pathogenic (score 0.7517) — an in-silico prediction, not a clinical call.

ELANE p.Pro42Ser

c.124C>T · VCV3761573

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7517 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,236)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7517	likely pathogenic
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -10.34	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 7.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 1,597,236). 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.Pro42Ser
Coding: c.124C>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852932 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 42: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

ELANE p.Pro42= Benign/Likely benign ★★ same residue
ELANE p.Pro42fs 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-pro42ser (accessed [today's date]).

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