Is ELANE p.Val45Ala (c.134T>C) pathogenic?

ELANE p.Val45Ala (c.134T>C) is classified Likely benign in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). AlphaMissense: likely benign (0.118); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Val45Ala (c.134T>C)?

ELANE p.Val45Ala (c.134T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Val45Ala (c.134T>C) in the general population?

ELANE p.Val45Ala (c.134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Val45Ala (c.134T>C)?

AlphaMissense predicts likely benign (score 0.118) — an in-silico prediction, not a clinical call.

ELANE p.Val45Ala

c.134T>C · VCV4842453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.118 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,284)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.118	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -4.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.41	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -1.9	GERP -4.7
Regional constraint	o/e 0.31	constrained · MANE · 62 bp · p 0.00023 · regional, not allelic
Overall
CADD	3.266	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

No allele count reported in gnomAD v4.1 (AN 1,597,284). 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.Val45Ala
Coding: c.134T>C
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852942 (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

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

Similar variants

ELANE p.Val45Leu Likely pathogenic ★ same residue
ELANE p.Val45Gly Uncertain significance ★ ⚠ same residue
ELANE p.Val45Met Uncertain significance ★ ⚠ same residue
ELANE p.Val45= Likely benign ★ same residue
ELANE p.Ala40Val Uncertain significance ★★ ⚠ same condition
ELANE p.Ala68Asp Uncertain significance ★★ ⚠ same condition
ELANE p.Ala79Thr Uncertain significance ★★ ⚠ same condition
ELANE p.Arg183Cys Uncertain significance ★★ ⚠ 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-val45ala (accessed [today's date]).

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