Is ALG13 p.Ser138fs (c.412dup) pathogenic?

ALG13 p.Ser138fs (c.412dup) is classified Likely pathogenic in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). Very rare (popmax 0.00279%, nfe); Associated with Seizure.

What condition is associated with ALG13 p.Ser138fs (c.412dup)?

ALG13 p.Ser138fs (c.412dup) is associated with Seizure (ClinVar).

How common is ALG13 p.Ser138fs (c.412dup) in the general population?

ALG13 p.Ser138fs (c.412dup) is very rare (popmax 0.00279%, nfe) (gnomAD).

ALG13 p.Ser138fs

c.412dup · rs2525558778 · VCV3242594

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00279%, nfe)

Conditions

Seizure

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 4 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 2, phastCons 0.83

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00279% European (non-Finnish) · 25/894,772 alleles

Filtering AF 0.00192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00207% 25/1,210,194 alleles · very rare exomes 25/1,096,603 · genomes 0/113,591 · 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: ALG13
Protein: p.Ser138fs
Coding: c.412dup
MANE Select: NM_001099922
dbSNP: rs2525558778
Type: Duplication
Location: chrX:111708054 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 138: the 'deubiquitinase activity' region

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Seizure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG13 c.1730-4A>T Uncertain significance same condition
ALG13 c.2458-34_2458dup Uncertain significance ★ same type
ALG13 p.Ala18dup Uncertain significance ★ same type
ALG13 p.Ala884dup Uncertain significance ★ same type
ALG13 p.Thr153fs Uncertain significance ★ same type
ALG13 c.1436-11dup Likely benign ★ same type
ALG13 c.1501-18dup Likely benign ★ same type
ALG13 c.2369-214dup Likely benign ★ same type

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/alg13-p-ser138fs (accessed [today's date]).

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