Is ALG13 p.Pro923= (c.2769A>C) pathogenic?

ALG13 p.Pro923= (c.2769A>C) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0612%, nfe); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro923= (c.2769A>C)?

ALG13 p.Pro923= (c.2769A>C) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro923= (c.2769A>C) in the general population?

ALG13 p.Pro923= (c.2769A>C) is ultra-rare (popmax 0.0612%, nfe) (gnomAD).

How is ALG13-CDG inherited?

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

ALG13 p.Pro923=

c.2769A>C · rs1602888164 · VCV756545

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0612%, nfe)

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 0.17	GERP -7, phastCons 0.007
Overall
CADD	0.188	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0612% European (non-Finnish) · 352/575,056 alleles

Filtering AF 0.0559% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0539%

Overall 0.0529% 411/776,706 alleles · ultra-rare exomes 402/695,514 · genomes 9/81,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0612%	1,634
Remaining individualsnot grpmax-eligible	0.0568%	1,762
Finnishnot grpmax-eligible	0.0503%	1,988
African / African-American	0.0357%	2,800
East Asian	0.0223%	4,484
Ashkenazi Jewishnot grpmax-eligible	0.0208%	4,809
South Asian	0.0107%	9,341
Admixed American	0.01%	9,988

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.Pro923=
Coding: c.2769A>C
MANE Select: NM_001099922
dbSNP: rs1602888164
Type: single nucleotide variant
Location: chrX:111744741 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 923: 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.Pro923Leu Uncertain significance ★★ ⚠ same residue
ALG13 p.Pro923Gln 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

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-pro923 (accessed [today's date]).

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