Is ALG13 p.Pro943Ala (c.2827C>G) pathogenic?

ALG13 p.Pro943Ala (c.2827C>G) is classified Uncertain significance in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). AlphaMissense: likely benign (0.0776); Very rare (popmax 0.000351%); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro943Ala (c.2827C>G)?

ALG13 p.Pro943Ala (c.2827C>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro943Ala (c.2827C>G) in the general population?

ALG13 p.Pro943Ala (c.2827C>G) is very rare (popmax 0.000351%) (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.Pro943Ala (c.2827C>G)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

ALG13 p.Pro943Ala

c.2827C>G · rs887315764 · VCV966978

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000351%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -10.46	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 0.001	GERP 2.1, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	7.277	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 0.000351%

Overall 0.000351% 4/1,139,457 alleles · very rare exomes 4/1,034,373 · genomes 0/105,084 · 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.Pro943Ala
Coding: c.2827C>G
MANE Select: NM_001099922
dbSNP: rs887315764
Type: single nucleotide variant
Location: chrX:111744799 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 943: 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.Pro943Ser Uncertain significance ★ ⚠ same residue
ALG13 p.Pro943_Ala946del Uncertain significance ★★ same residue
ALG13 p.Pro943_Pro945del Likely benign ★ same residue
ALG13 p.Pro943_Pro945dup 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

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-pro943ala (accessed [today's date]).

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