Is ALG13 p.Ala916= (c.2748C>G) pathogenic?

ALG13 p.Ala916= (c.2748C>G) is classified Likely benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Very rare (popmax 0.00393%, sas); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ala916= (c.2748C>G)?

ALG13 p.Ala916= (c.2748C>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ala916= (c.2748C>G) in the general population?

ALG13 p.Ala916= (c.2748C>G) is very rare (popmax 0.00393%, sas) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Ala916=

c.2748C>G · rs1944057747 · VCV2744702

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00393%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.73	GERP 0.17
Overall
CADD	0.854	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00393% South Asian · 2/50,897 alleles

Filtering AF 0.000652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000244%

Overall 0.000172% 2/1,160,946 alleles · very rare exomes 2/1,053,198 · genomes 0/107,748 · 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.Ala916=
Coding: c.2748C>G
MANE Select: NM_001099922
dbSNP: rs1944057747
Type: single nucleotide variant
Location: chrX:111744720 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 916: the 'disordered' 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-ala916 (accessed [today's date]).

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