Is ALG13 p.Ala384= (c.1152G>A) pathogenic?

ALG13 p.Ala384= (c.1152G>A) is classified Benign/Likely benign in ALG13 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.98%, afr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ala384= (c.1152G>A)?

ALG13 p.Ala384= (c.1152G>A) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ala384= (c.1152G>A) in the general population?

ALG13 p.Ala384= (c.1152G>A) is low-frequency (popmax 1.98%, afr) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Ala384=

c.1152G>A · rs145353928 · VCV382137

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.98%, afr)

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.15	GERP 3.3, phastCons 0.001
Overall
CADD	3.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.98% African / African-American · 1,108/56,044 alleles

Filtering AF 1.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.84%

Overall 0.116% 1,355/1,168,749 alleles · low-frequency exomes 684/1,056,957 · genomes 671/111,792 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.98%	51
Admixed American	0.204%	489
Remaining individualsnot grpmax-eligible	0.113%	887
Middle Eastern	0.0699%	1,430
European (non-Finnish)	0.0128%	7,792

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.Ala384=
Coding: c.1152G>A
MANE Select: NM_001099922
dbSNP: rs145353928
Type: single nucleotide variant
Location: chrX:111718176 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 384: the 'deubiquitinase activity' region

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

Disease context

developmental and epileptic encephalopathy, 36 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG13-CDG (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG13 c.2458-1G>A Uncertain significance ★★ same condition
ALG13 c.2695+4G>A Uncertain significance ★★ same condition
ALG13 c.2932+6T>C Uncertain significance ★★ same condition
ALG13 c.834+3A>G Uncertain significance ★★ same condition
ALG13 c.932+2T>C Uncertain significance ★★ same condition
ALG13 p.Ala1044Thr Uncertain significance ★★ ⚠ same condition
ALG13 p.Ala173Val 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/alg13-p-ala384 (accessed [today's date]).

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