Is ALG13 p.Ser693Phe (c.2078C>T) pathogenic?

ALG13 p.Ser693Phe (c.2078C>T) is classified Uncertain significance in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-13). AlphaMissense: likely benign (0.2327); Very rare (popmax 0.000338%, nfe); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Ser693Phe (c.2078C>T)?

ALG13 p.Ser693Phe (c.2078C>T) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Ser693Phe (c.2078C>T) in the general population?

ALG13 p.Ser693Phe (c.2078C>T) is very rare (popmax 0.000338%, 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.Ser693Phe (c.2078C>T)?

AlphaMissense predicts likely benign (score 0.2327) — an in-silico prediction, not a clinical call.

ALG13 p.Ser693Phe

c.2078C>T · rs919912146 · VCV647916

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000338%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.2327	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -8.73	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 5.4	GERP 4.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000338% European (non-Finnish) · 3/887,086 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.00025% 3/1,199,300 alleles · very rare exomes 1/1,087,601 · genomes 2/111,699 · 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.Ser693Phe
Coding: c.2078C>T
MANE Select: NM_001099922
dbSNP: rs919912146
Type: single nucleotide variant
Location: chrX:111727433 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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.Ser693Thr 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-ser693phe (accessed [today's date]).

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