Is ALG2 p.Gly72Val (c.215G>T) pathogenic?

ALG2 p.Gly72Val (c.215G>T) is classified Uncertain significance in ALG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.8777); Ultra-rare (popmax 0.0509%, amr); Associated with ALG2-congenital disorder of glycosylation.

What condition is associated with ALG2 p.Gly72Val (c.215G>T)?

ALG2 p.Gly72Val (c.215G>T) is associated with ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Gly72Val (c.215G>T) in the general population?

ALG2 p.Gly72Val (c.215G>T) is ultra-rare (popmax 0.0509%, amr) (gnomAD).

How is ALG2-CDG inherited?

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

What do computational predictors say about ALG2 p.Gly72Val (c.215G>T)?

AlphaMissense predicts likely pathogenic (score 0.8777) — an in-silico prediction, not a clinical call.

ALG2 p.Gly72Val

c.215G>T · rs770738799 · VCV941497

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8777 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG2-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.8777	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,957 bp · p 0.038 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.0509% Admixed American · 28/54,988 alleles

Filtering AF 0.0362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00179% 28/1,566,546 alleles · ultra-rare

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.Gly72Val
Coding: c.215G>T
MANE Select: NM_033087
dbSNP: rs770738799
Type: single nucleotide variant
Location: chr9:99221680 (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

ALG2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 14

For ALG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG2 p.Gly72Arg Uncertain significance ★ ⚠ same residue
ALG2 p.Gly72= Likely benign ★ same residue
ALG2 p.Gly72_Leu75delinsSerProArg Pathogenic/Likely pathogenic ★★ same residue
ALG2 p.Gly72fs Pathogenic 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

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-gly72val (accessed [today's date]).

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