Is ALS2 p.Asp1298fs (c.3893del) pathogenic?

ALS2 p.Asp1298fs (c.3893del) is classified Likely pathogenic in ALS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). Absent from gnomAD; Associated with amyotrophic lateral sclerosis type 2, juvenile.

What condition is associated with ALS2 p.Asp1298fs (c.3893del)?

ALS2 p.Asp1298fs (c.3893del) is associated with amyotrophic lateral sclerosis type 2, juvenile (ClinVar).

How common is ALS2 p.Asp1298fs (c.3893del) in the general population?

ALS2 p.Asp1298fs (c.3893del) is absent from gnomAD (gnomAD).

How is Juvenile amyotrophic lateral sclerosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALS2 p.Asp1298fs

c.3893del · rs2469724450 · VCV2444046

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

amyotrophic lateral sclerosis type 2, juvenile

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 25 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP -3.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALS2
Protein: p.Asp1298fs
Coding: c.3893del
MANE Select: NM_020919
dbSNP: rs2469724450
Type: Deletion
Location: chr2:201715783 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.69

Full ALS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amyotrophic lateral sclerosis type 2, juvenile — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Juvenile amyotrophic lateral sclerosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ALS2 p.Leu623fs Pathogenic ★★ same condition
ALS2 p.Gln1355fs Likely pathogenic ★ same condition
ALS2 p.Ile441fs Likely pathogenic ★ same condition
ALS2 p.Thr185fs Pathogenic ★ same condition
ALS2 p.Asp1298= Likely benign ★ same residue
ALS2 p.Ala47fs Pathogenic same condition
ALS2 c.2580+2T>C Pathogenic ★★ same condition
ALS2 c.4626+1G>A Pathogenic/Likely pathogenic ★★ 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/als2-p-asp1298fs (accessed [today's date]).

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