Is ALG13 p.Cys182Ser (c.544T>A) pathogenic?

ALG13 p.Cys182Ser (c.544T>A) is classified Likely benign in ALG13 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1327); Ultra-rare (popmax 0.0347%, amr); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Cys182Ser (c.544T>A)?

ALG13 p.Cys182Ser (c.544T>A) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Cys182Ser (c.544T>A) in the general population?

ALG13 p.Cys182Ser (c.544T>A) is ultra-rare (popmax 0.0347%, amr) (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.Cys182Ser (c.544T>A)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

ALG13 p.Cys182Ser

c.544T>A · rs778876158 · VCV1122898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1327	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -4.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	14.52	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

Grpmax group 0.0347% Admixed American · 16/46,044 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00132% 16/1,211,739 alleles · ultra-rare exomes 16/1,097,987 · genomes 0/113,752 · 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.Cys182Ser
Coding: c.544T>A
MANE Select: NM_001099922
dbSNP: rs778876158
Type: single nucleotide variant
Location: chrX:111708187 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 182: 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-cys182ser (accessed [today's date]).

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