Is ELANE p.Ala40Val (c.119C>T) pathogenic?

ELANE p.Ala40Val (c.119C>T) is classified Uncertain significance in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-04). AlphaMissense: likely benign (0.2956); Very rare (popmax 0.00168%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala40Val (c.119C>T)?

ELANE p.Ala40Val (c.119C>T) is associated with Inborn genetic diseases, cyclic neutropenia, neutropenia, severe congenital, 1, autosomal dominant (ClinVar).

How common is ELANE p.Ala40Val (c.119C>T) in the general population?

ELANE p.Ala40Val (c.119C>T) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about ELANE p.Ala40Val (c.119C>T)?

AlphaMissense predicts likely benign (score 0.2956) — an in-silico prediction, not a clinical call.

ELANE p.Ala40Val

c.119C>T · rs1555709342 · VCV467828

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2956	likely benign
REVEL	0.549	indeterminate
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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	24.1	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

Grpmax group 0.00168% Admixed American · 1/59,664 alleles

Overall 0.000657% 1/152,216 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ELANE
Protein: p.Ala40Val
Coding: c.119C>T
MANE Select: NM_001972
dbSNP: rs1555709342
Type: single nucleotide variant
Location: chr19:852927 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 40: 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.Ala40Thr Uncertain significance ★ ⚠ same residue
ELANE p.Ala40= 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

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-ala40val (accessed [today's date]).

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