Is ELANE p.Asp230Asn (c.688G>A) pathogenic?

ELANE p.Asp230Asn (c.688G>A) is classified Conflicting classifications of pathogenicity in ELANE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.7891); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Asp230Asn (c.688G>A)?

ELANE p.Asp230Asn (c.688G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Asp230Asn (c.688G>A) in the general population?

ELANE p.Asp230Asn (c.688G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ELANE p.Asp230Asn (c.688G>A)?

AlphaMissense predicts likely pathogenic (score 0.7891) — an in-silico prediction, not a clinical call.

ELANE p.Asp230Asn

c.688G>A · rs747904347 · VCV2648869

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7891	likely pathogenic
REVEL	0.455	indeterminate
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,171 bp · p 0.52 · regional, not allelic
Overall
CADD	23.9	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000958% 14/1,461,166 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
European (non-Finnish)	0.000932%	107,270

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.Asp230Asn
Coding: c.688G>A
MANE Select: NM_001972
dbSNP: rs747904347
Type: single nucleotide variant
Location: chr19:856048 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.42 · 38 PDB
Residue 230: a β-strand; 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.Asp230His 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
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-asp230asn (accessed [today's date]).

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