Is ELANE p.Phe54Val (c.160T>G) pathogenic?

ELANE p.Phe54Val (c.160T>G) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). AlphaMissense: likely pathogenic (0.6534); Absent from gnomAD v4.1; Associated with neutropenia, severe congenital, 1, autosomal dominant.

What condition is associated with ELANE p.Phe54Val (c.160T>G)?

ELANE p.Phe54Val (c.160T>G) is associated with neutropenia, severe congenital, 1, autosomal dominant, cyclic neutropenia (ClinVar).

How common is ELANE p.Phe54Val (c.160T>G) in the general population?

ELANE p.Phe54Val (c.160T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Phe54Val (c.160T>G)?

AlphaMissense predicts likely pathogenic (score 0.6534) — an in-silico prediction, not a clinical call.

ELANE p.Phe54Val

Q: How is Autosomal dominant severe congenital neutropenia inherited?

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

c.160T>G · VCV4783765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6534 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neutropenia, severe congenital, 1, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.6534	likely pathogenic
REVEL	0.561	indeterminate
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -0.5, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	21.7	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.Phe54Val
Coding: c.160T>G
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852968 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 54: a β-strand; the peptidase s1 domain

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.Phe54= 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
ELANE p.Ala61Val Pathogenic/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-phe54val (accessed [today's date]).

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