Is ALG2 p.Ala61= (c.183C>T) pathogenic?

ALG2 p.Ala61= (c.183C>T) is classified Likely benign in ALG2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00407%, nfe); Associated with congenital myasthenic syndrome 14.

What condition is associated with ALG2 p.Ala61= (c.183C>T)?

ALG2 p.Ala61= (c.183C>T) is associated with congenital myasthenic syndrome 14, ALG2-congenital disorder of glycosylation (ClinVar).

How common is ALG2 p.Ala61= (c.183C>T) in the general population?

ALG2 p.Ala61= (c.183C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

How is ALG2-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALG2 p.Ala61=

c.183C>T · rs755793459 · VCV1666006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Conditions

congenital myasthenic syndrome 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3
Overall
CADD	6.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,178,006 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00307% 49/1,595,586 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,542
African / African-American	0.00134%	74,758

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: ALG2
Protein: p.Ala61=
Coding: c.183C>T
MANE Select: NM_033087
dbSNP: rs755793459
Type: single nucleotide variant
Location: chr9:99221712 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full ALG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG2-congenital disorder of glycosylation

For ALG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG2 p.Ala61Val Uncertain significance ★ ⚠ same residue
ALG2 p.Ala29Pro Uncertain significance ★★ ⚠ same condition
ALG2 p.Ala36Val Uncertain significance ★★ ⚠ same condition
ALG2 p.Ala71Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Ala71Val Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg129Gln Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg130Gln Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg251His 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/alg2-p-ala61 (accessed [today's date]).

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