Is ALG13 p.Phe284Leu (c.852T>G) pathogenic?

ALG13 p.Phe284Leu (c.852T>G) is classified Uncertain significance in ALG13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-18). AlphaMissense: likely pathogenic (0.9818); No allele count reported in gnomAD v4.1 (AN 1,209,060); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Phe284Leu (c.852T>G)?

ALG13 p.Phe284Leu (c.852T>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Phe284Leu (c.852T>G) in the general population?

ALG13 p.Phe284Leu (c.852T>G) is no allele count reported in gnomAD v4.1 (AN 1,209,060) (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.Phe284Leu (c.852T>G)?

AlphaMissense predicts likely pathogenic (score 0.9818) — an in-silico prediction, not a clinical call.

ALG13 p.Phe284Leu

c.852T>G · rs2525630932 · VCV3012363

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9818 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,209,060)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.9818	likely pathogenic · top 4% in ALG13
REVEL	0.257	benign-leaning
SaProt	LLR -10.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,848 bp · p 0.46 · regional, not allelic
Overall
CADD	21.4	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

No allele count reported in gnomAD v4.1 (AN 1,209,060). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG13
Protein: p.Phe284Leu
Coding: c.852T>G
MANE Select: NM_001099922
dbSNP: rs2525630932
Type: single nucleotide variant
Location: chrX:111711692 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 284: 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.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
ALG13 p.Ala173Val 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-phe284leu (accessed [today's date]).

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