Is ELANE p.Val101Gly (c.302T>G) pathogenic?

ELANE p.Val101Gly (c.302T>G) is classified Pathogenic in ELANE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.7966); Absent from gnomAD v4.1; Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Val101Gly (c.302T>G)?

ELANE p.Val101Gly (c.302T>G) is associated with neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Val101Gly (c.302T>G) in the general population?

ELANE p.Val101Gly (c.302T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Val101Gly (c.302T>G)?

AlphaMissense predicts likely pathogenic (score 0.7966) — an in-silico prediction, not a clinical call.

ELANE p.Val101Gly

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.302T>G · VCV4076136

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.7966	likely pathogenic ✓ concordant with ClinVar
REVEL	0.396	indeterminate
SaProt	LLR -13.68	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 7.6	GERP 1.3, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	22.4	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.Val101Gly
Coding: c.302T>G
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:853339 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 101: a β-strand; the peptidase s1 domain; a UniProt-annotated variant site (in scn1; located on the same allele as l-98; reduces proteolytic enzyme activity by slightly less than half; together with l-98 shows an additive effect with minimal remaining enzyme activity); 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

For Autosomal dominant severe congenital neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ELANE p.Val101Met Pathogenic ★★ same residue
ELANE p.Val101fs Uncertain significance ★★ same residue
ELANE p.Val101= Benign/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-val101gly (accessed [today's date]).

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