Is ALG13 p.Pro943Ser (c.2827C>T) pathogenic?

ALG13 p.Pro943Ser (c.2827C>T) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). AlphaMissense: likely benign (0.1034); Very rare (popmax 0.000117%, nfe); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro943Ser (c.2827C>T)?

ALG13 p.Pro943Ser (c.2827C>T) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro943Ser (c.2827C>T) in the general population?

ALG13 p.Pro943Ser (c.2827C>T) is very rare (popmax 0.000117%, nfe) (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.Pro943Ser (c.2827C>T)?

AlphaMissense predicts likely benign (score 0.1034) — an in-silico prediction, not a clinical call.

ALG13 p.Pro943Ser

c.2827C>T · rs887315764 · VCV2697883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1034 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000117%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1034	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -10.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	6.798	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 0.000117% European (non-Finnish) · 1/855,383 alleles

Overall 0.000176% 2/1,139,457 alleles · very rare exomes 2/1,034,373 · genomes 0/105,084 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00222%	44,990
European (non-Finnish)grpmax	0.000117%	855,381

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro943Ser
Coding: c.2827C>T
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.Pro943Ala 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-pro943ser (accessed [today's date]).

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