Is ALG13 p.Leu251= (c.751T>C) pathogenic?

ALG13 p.Leu251= (c.751T>C) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). No allele count reported in gnomAD v4.1 (AN 1,172,623); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Leu251= (c.751T>C)?

ALG13 p.Leu251= (c.751T>C) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Leu251= (c.751T>C) in the general population?

ALG13 p.Leu251= (c.751T>C) is no allele count reported in gnomAD v4.1 (AN 1,172,623) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Leu251=

c.751T>C · rs780004678 · VCV2962032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,172,623)

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	all four deltas below 0.2 · T>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.2	GERP 4.9, phastCons 1
Overall
CADD	13.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,172,623). 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: ALG13
Protein: p.Leu251=
Coding: c.751T>C
MANE Select: NM_001099922
dbSNP: rs780004678
Type: single nucleotide variant
Location: chrX:111708965 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 251: the otu domain; 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-leu251 (accessed [today's date]).

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