Is ALG13 p.Glu69Asp (c.207A>C) pathogenic?

ALG13 p.Glu69Asp (c.207A>C) is classified Conflicting classifications of pathogenicity in ALG13 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.1122); Very rare (popmax 0.00529%, afr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Glu69Asp (c.207A>C)?

ALG13 p.Glu69Asp (c.207A>C) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Glu69Asp (c.207A>C) in the general population?

ALG13 p.Glu69Asp (c.207A>C) is very rare (popmax 0.00529%, afr) (gnomAD).

How is ALG13-CDG inherited?

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

What do computational predictors say about ALG13 p.Glu69Asp (c.207A>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

ALG13 p.Glu69Asp

c.207A>C · rs745826764 · VCV1055204

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00529%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	GERP -0.81, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	18.68	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00529% African / African-American · 3/56,725 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.000419% 5/1,193,437 alleles · very rare exomes 4/1,081,201 · genomes 1/112,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00529%	18,908
Remaining individualsnot grpmax-eligible	0.00427%	23,430

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.Glu69Asp
Coding: c.207A>C
MANE Select: NM_001099922
dbSNP: rs745826764
Type: single nucleotide variant
Location: chrX:111682257 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 69: 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-glu69asp (accessed [today's date]).

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