Is ALG13 p.Pro923Gln (c.2768C>A) pathogenic?

ALG13 p.Pro923Gln (c.2768C>A) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely benign (0.1397); Very rare (popmax 9.63e-05%); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro923Gln (c.2768C>A)?

ALG13 p.Pro923Gln (c.2768C>A) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro923Gln (c.2768C>A) in the general population?

ALG13 p.Pro923Gln (c.2768C>A) is very rare (popmax 9.63e-05%) (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.Pro923Gln (c.2768C>A)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

ALG13 p.Pro923Gln

c.2768C>A · rs1047232159 · VCV2108353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.63e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -13.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.05, phastCons 0.14
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	9.885	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 9.63e-05%

Overall 9.63e-05% 1/1,037,893 alleles · very rare exomes 1/942,469 · genomes 0/95,424 · 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.Pro923Gln
Coding: c.2768C>A
MANE Select: NM_001099922
dbSNP: rs1047232159
Type: single nucleotide variant
Location: chrX:111744740 (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.Pro923= Likely benign ★★ 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-pro923gln (accessed [today's date]).

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