Is ELANE p.Val45Leu (c.133G>C) pathogenic?

ELANE p.Val45Leu (c.133G>C) is classified Likely pathogenic in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.7837); Absent from gnomAD v4.1; Associated with ELANE-related disorder.

What condition is associated with ELANE p.Val45Leu (c.133G>C)?

ELANE p.Val45Leu (c.133G>C) is associated with ELANE-related disorder (ClinVar).

How common is ELANE p.Val45Leu (c.133G>C) in the general population?

ELANE p.Val45Leu (c.133G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Val45Leu (c.133G>C)?

AlphaMissense predicts likely pathogenic (score 0.7837) — an in-silico prediction, not a clinical call.

ELANE p.Val45Leu

c.133G>C · rs1599290793 · VCV2632170

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ELANE-related disorder

Computational evidence

Protein change
AlphaMissense	0.7837	likely pathogenic ✓ concordant with ClinVar
REVEL	0.639	indeterminate
SaProt	LLR -11.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	23.6	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.Val45Leu
Coding: c.133G>C
MANE Select: NM_001972
dbSNP: rs1599290793
Type: single nucleotide variant
Location: chr19:852941 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 45: a β-strand; a UniProt-annotated variant site (in scn1); a UniProt-annotated variant site (in ch); the peptidase s1 domain

Full ELANE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ELANE-related disorder

Similar variants

ELANE p.Val45Gly Uncertain significance ★ ⚠ same residue
ELANE p.Val45Met Uncertain significance ★ ⚠ same residue
ELANE p.Val45= Likely benign ★ same residue
ELANE p.Val45Ala Likely benign ★ same residue
ELANE c.597+1G>T Pathogenic ★★ same condition
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg103Leu Likely pathogenic ★★ ⚠ same condition
ELANE p.Arg220Gln 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-val45leu (accessed [today's date]).

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