Is ALG13 p.Ser343Cys (c.1027A>T) pathogenic?

ALG13 p.Ser343Cys (c.1027A>T) is classified Likely benign in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-24). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ser343Cys (c.1027A>T)?

ALG13 p.Ser343Cys (c.1027A>T) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ser343Cys (c.1027A>T) in the general population?

ALG13 p.Ser343Cys (c.1027A>T) is absent from gnomAD v4.1 (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.Ser343Cys (c.1027A>T)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

ALG13 p.Ser343Cys

c.1027A>T · rs2525736764 · VCV2158863

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,848 bp · p 0.46 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG13
Protein: p.Ser343Cys
Coding: c.1027A>T
MANE Select: NM_001099922
dbSNP: rs2525736764
Type: single nucleotide variant
Location: chrX:111717867 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 343: the otu domain; the 'deubiquitinase activity' 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.Ser343= Conflicting classifications of pathogenicity ★ same residue
ALG13 p.Ser343Asn 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-ser343cys (accessed [today's date]).

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