Is ALG13 p.Ser21Trp (c.62C>G) pathogenic?

ALG13 p.Ser21Trp (c.62C>G) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: ambiguous (0.4272); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ser21Trp (c.62C>G)?

ALG13 p.Ser21Trp (c.62C>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ser21Trp (c.62C>G) in the general population?

ALG13 p.Ser21Trp (c.62C>G) 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.Ser21Trp (c.62C>G)?

AlphaMissense predicts ambiguous (score 0.4272) — an in-silico prediction, not a clinical call.

ALG13 p.Ser21Trp

c.62C>G · rs1602457991 · VCV1963721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4272 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.4272	ambiguous
REVEL	0.408	indeterminate
SaProt	LLR -10.17	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.16	GERP -1.8, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	21.6	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.Ser21Trp
Coding: c.62C>G
MANE Select: NM_001099922
dbSNP: rs1602457991
Type: single nucleotide variant
Location: chrX:111681280 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 21: the 'glycosyltransferase 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.Ser21Leu 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
ALG13 p.Ala1044Thr 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-ser21trp (accessed [today's date]).

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