Is ALG13 p.Met269Val (c.805A>G) pathogenic?

ALG13 p.Met269Val (c.805A>G) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely pathogenic (0.6436); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Met269Val (c.805A>G)?

ALG13 p.Met269Val (c.805A>G) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Met269Val (c.805A>G) in the general population?

ALG13 p.Met269Val (c.805A>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.Met269Val (c.805A>G)?

AlphaMissense predicts likely pathogenic (score 0.6436) — an in-silico prediction, not a clinical call.

ALG13 p.Met269Val

c.805A>G · rs2525581314 · VCV2961626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6436 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.6436	likely pathogenic
REVEL	0.243	benign-leaning
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 4.3, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 698 bp · p 5.1e-05 · regional, not allelic
Overall
CADD	21.2	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.Met269Val
Coding: c.805A>G
MANE Select: NM_001099922
dbSNP: rs2525581314
Type: single nucleotide variant
Location: chrX:111709019 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 269: 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-met269val (accessed [today's date]).

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