Is ALG13 p.Gln273= (c.819A>G) pathogenic?

ALG13 p.Gln273= (c.819A>G) is classified Likely benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). Ultra-rare (popmax 0.0237%, mid); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Gln273= (c.819A>G)?

ALG13 p.Gln273= (c.819A>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Gln273= (c.819A>G) in the general population?

ALG13 p.Gln273= (c.819A>G) is ultra-rare (popmax 0.0237%, mid) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Gln273=

c.819A>G · rs774384951 · VCV1078556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, mid)

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 1.8	GERP 5.4, phastCons 0.99
Overall
CADD	7.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0237% Middle Eastern · 1/4,221 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000164%

Overall 0.00137% 16/1,170,110 alleles · ultra-rare exomes 16/1,056,437 · genomes 0/113,673 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0285%	3,511
Middle Easterngrpmax	0.0237%	4,221
Remaining individualsnot grpmax-eligible	0.00655%	15,268
European (non-Finnish)	0.000692%	144,498

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln273=
Coding: c.819A>G
MANE Select: NM_001099922
dbSNP: rs774384951
Type: single nucleotide variant
Location: chrX:111709033 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 273: 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.Gln273Pro Uncertain significance ★★ ⚠ same residue
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

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-gln273 (accessed [today's date]).

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