Is ELANE p.Arg5Cys (c.13C>T) pathogenic?

ELANE p.Arg5Cys (c.13C>T) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-04). AlphaMissense: likely benign (0.2693); Very rare (popmax 0.000339%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with ELANE p.Arg5Cys (c.13C>T)?

ELANE p.Arg5Cys (c.13C>T) is associated with autoinflammatory syndrome (ClinVar).

How common is ELANE p.Arg5Cys (c.13C>T) in the general population?

ELANE p.Arg5Cys (c.13C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ELANE p.Arg5Cys (c.13C>T)?

AlphaMissense predicts likely benign (score 0.2693) — an in-silico prediction, not a clinical call.

ELANE p.Arg5Cys

c.13C>T · rs942026381 · VCV1694265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
AlphaMissense	0.2693	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.7	GERP -3.3
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	4.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,852 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,610,116 alleles · very rare exomes 3/1,457,944 · genomes 1/152,172 · joint denominator

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.Arg5Cys
Coding: c.13C>T
MANE Select: NM_001972
dbSNP: rs942026381
Type: single nucleotide variant
Location: chr19:852341 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELANE p.Arg5Leu Uncertain significance ★★ ⚠ same residue
ELANE p.Arg5Gly Uncertain significance ★ ⚠ same residue
ELANE p.Arg5His Conflicting classifications of pathogenicity ★ ⚠ same residue
ELANE p.Arg5= Likely benign ★ same residue
ELANE p.Ala61Val Pathogenic/Likely pathogenic ★★ same condition
ELANE p.Arg92Gln Uncertain significance ★★ ⚠ same condition
ELANE p.Gly148Arg Uncertain significance ★★ same condition
ELANE p.Gly226Arg 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-arg5cys (accessed [today's date]).

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