Is ELANE p.Asn76= (c.228C>T) pathogenic?

ELANE p.Asn76= (c.228C>T) is classified Likely benign in ELANE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-22). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Asn76= (c.228C>T)?

ELANE p.Asn76= (c.228C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Asn76= (c.228C>T) in the general population?

ELANE p.Asn76= (c.228C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

ELANE p.Asn76=

c.228C>T · VCV3844328

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.036	GERP -2.8, phastCons 0.001
Overall
CADD	4.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,382 alleles

Overall 0.000657% 1/152,214 alleles · very 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.Asn76=
Coding: c.228C>T
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:853265 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 76: 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.Asn76Ser Uncertain significance ★ ⚠ same residue
ELANE p.Asn76Thr Uncertain significance ★ ⚠ same residue
ELANE p.Asn76Lys 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-asn76 (accessed [today's date]).

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