Is ALG13 p.Pro945del (c.2797CCT[12]) pathogenic?

ALG13 p.Pro945del (c.2797CCT[12]) is classified Benign in ALG13 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro945del (c.2797CCT[12])?

ALG13 p.Pro945del (c.2797CCT[12]) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How is ALG13-CDG inherited?

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

ALG13 p.Pro945del

Q: How common is ALG13 p.Pro945del (c.2797CCT[12]) in the general population?

ALG13 p.Pro945del (c.2797CCT[12]) is common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2797CCT[12] · rs56717389 · VCV238295

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele

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 · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP 0.19
Overall
CADD	0.256	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(ACC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.1% African / African-American · 2,530/20,920 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 4.83% 22,031/455,685 alleles · common exomes 20,634/418,670 · genomes 1,397/37,015 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.1%	8
Ashkenazi Jewishnot grpmax-eligible	7.62%	13
Admixed American	6.42%	16
Remaining individualsnot grpmax-eligible	5.86%	17
East Asian	5.56%	18
South Asian	5.38%	19
European (non-Finnish)	4.27%	23
Middle Eastern	4.15%	24
Finnishnot grpmax-eligible	2.85%	35

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.Pro945del
Coding: c.2797CCT[12]
MANE Select: NM_001099922
dbSNP: rs56717389
Type: Microsatellite
Location: chrX:111744769 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 945: 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.Pro945_Ala946insProProProProPro Uncertain significance ★ same residue
ALG13 p.Pro945_Ala946insProProProProProProPro Uncertain significance ★ same residue
ALG13 p.Pro945= Likely benign ★ same residue
ALG13 p.Pro945_Ala946insPro Likely benign ★ same residue
ALG13 p.Pro945_Ala946insProProPro Likely benign ★ same residue
ALG13 p.Pro945dup Likely benign ★ same residue
ALG13 c.2457+15_2457+17del Benign/Likely benign ★★ same condition
ALG13 c.751-8_751-6del Benign/Likely benign ★★ 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-pro945del (accessed [today's date]).

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