Is ELANE p.Asn147Lys (c.441C>G) pathogenic?

ELANE p.Asn147Lys (c.441C>G) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.383); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Asn147Lys (c.441C>G)?

ELANE p.Asn147Lys (c.441C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Asn147Lys (c.441C>G) in the general population?

ELANE p.Asn147Lys (c.441C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELANE p.Asn147Lys (c.441C>G)?

AlphaMissense predicts ambiguous (score 0.383) — an in-silico prediction, not a clinical call.

ELANE p.Asn147Lys

c.441C>G · rs146878885 · VCV2552413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.383 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.383	ambiguous
REVEL	0.451	indeterminate
SaProt	LLR -10.98	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.5	GERP -4.3
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	0.002	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.Asn147Lys
Coding: c.441C>G
MANE Select: NM_001972
dbSNP: rs146878885
Type: single nucleotide variant
Location: chr19:855638 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 147: 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.Asn147Ser Uncertain significance ★ ⚠ same residue
ELANE p.Asn147= 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
ELANE p.Arg248His Uncertain significance ★★ ⚠ same condition
ELANE p.Arg78Leu 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-asn147lys (accessed [today's date]).

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