Is ALG14 p.Trp115del (c.342_344del) pathogenic?

ALG14 p.Trp115del (c.342344del) is classified Uncertain significance in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-03). Very rare (popmax 0.000424%, nfe); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Trp115del (c.342_344del)?

ALG14 p.Trp115del (c.342_344del) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Trp115del (c.342_344del) in the general population?

ALG14 p.Trp115del (c.342_344del) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Congenital myasthenic syndrome inherited?

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

ALG14 p.Trp115del

c.342_344del · rs1210554241 · VCV1046647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,958 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,820 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: ALG14
Protein: p.Trp115del
Coding: c.342_344del
MANE Select: NM_144988
dbSNP: rs1210554241
Type: Deletion
Location: chr1:95027205 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 115: a UniProt-annotated variant site (in cms15)

Full ALG14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ALG14 c.421-19del Likely benign ★ same condition
ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn82Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu179Lys 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/alg14-p-trp115del (accessed [today's date]).

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