Is ELANE p.Arg183His (c.548G>A) pathogenic?

ELANE p.Arg183His (c.548G>A) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.1634); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Arg183His (c.548G>A)?

ELANE p.Arg183His (c.548G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Arg183His (c.548G>A) in the general population?

ELANE p.Arg183His (c.548G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELANE p.Arg183His (c.548G>A)?

AlphaMissense predicts likely benign (score 0.1634) — an in-silico prediction, not a clinical call.

ELANE p.Arg183His

c.548G>A · VCV3844286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1634	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -10.48	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 0.038	GERP -4.3
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	17.34	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 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000311% 5/1,609,376 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,388
European (non-Finnish)	0.000254%	393,315

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.Arg183His
Coding: c.548G>A
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:855745 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 183: a disulfide bond; 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.Arg183Cys Uncertain significance ★★ ⚠ same residue
ELANE p.Arg183= 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.Arg248His Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Leu Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Ser 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-arg183his (accessed [today's date]).

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