Is ELANE p.His39Arg (c.116A>G) pathogenic?

ELANE p.His39Arg (c.116A>G) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: ambiguous (0.4501); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.His39Arg (c.116A>G)?

ELANE p.His39Arg (c.116A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.His39Arg (c.116A>G) in the general population?

ELANE p.His39Arg (c.116A>G) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ELANE p.His39Arg (c.116A>G)?

AlphaMissense predicts ambiguous (score 0.4501) — an in-silico prediction, not a clinical call.

ELANE p.His39Arg

c.116A>G · VCV4618408

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4501 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4501	ambiguous
REVEL	0.642	indeterminate
SaProt	LLR -9.49	tolerated
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 10	GERP 0.57, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	18.79	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 0.0167% Middle Eastern · 1/6,000 alleles

Overall 6.92e-05% 1/1,444,334 alleles · ultra-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.His39Arg
Coding: c.116A>G
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852924 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 39: 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.His39= Likely benign ★★ same residue
ELANE p.His39Tyr Uncertain significance ★ ⚠ same residue
ELANE p.His39Gln Uncertain significance ★★ ⚠ 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
ELANE p.Arg248His 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-his39arg (accessed [today's date]).

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