Is ELANE p.Ala13Asp (c.38C>A) pathogenic?

ELANE p.Ala13Asp (c.38C>A) is classified Uncertain significance in ELANE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.4928); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with ELANE p.Ala13Asp (c.38C>A)?

ELANE p.Ala13Asp (c.38C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELANE p.Ala13Asp (c.38C>A) in the general population?

ELANE p.Ala13Asp (c.38C>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ELANE p.Ala13Asp (c.38C>A)?

AlphaMissense predicts ambiguous (score 0.4928) — an in-silico prediction, not a clinical call.

ELANE p.Ala13Asp

c.38C>A · VCV4618409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4928	ambiguous
REVEL	0.544	indeterminate
SaProt	LLR -10.21	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Regional constraint	o/e 1.02	unconstrained · MANE · 597 bp · p 0.86 · regional, not allelic
Overall
CADD	8.884	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 0.004% African / African-American · 3/74,926 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,611,540 alleles · very rare exomes 2/1,459,342 · genomes 1/152,198 · 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.Ala13Asp
Coding: c.38C>A
MANE Select: NM_001972
Type: single nucleotide variant
Location: chr19:852366 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELANE p.Ala13Thr Uncertain significance ★ ⚠ same residue
ELANE p.Ala13= Likely benign ★ same residue
ELANE p.Ala13Ser Uncertain significance ★★ ⚠ same residue
ELANE p.Ala13Gly 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

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-ala13asp (accessed [today's date]).

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