Is ALG13 p.Thr53= (c.159T>C) pathogenic?

ALG13 p.Thr53= (c.159T>C) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-21). Ultra-rare (popmax 0.0231%, mid); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Thr53= (c.159T>C)?

ALG13 p.Thr53= (c.159T>C) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Thr53= (c.159T>C) in the general population?

ALG13 p.Thr53= (c.159T>C) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Thr53=

c.159T>C · rs1933618884 · VCV1934940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.39	acceptor loss · deltas
Pangolin	Δ0.24	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% Middle Eastern · 1/4,321 alleles

Overall 8.31e-05% 1/1,203,686 alleles · ultra-rare exomes 1/1,089,693 · genomes 0/113,993 · 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.Thr53=
Coding: c.159T>C
MANE Select: NM_001099922
dbSNP: rs1933618884
Type: single nucleotide variant
Location: chrX:111682209 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 53: the 'glycosyltransferase 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-thr53 (accessed [today's date]).

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