Is ALG2 p.Gly78Arg (c.232G>C) pathogenic?

ALG2 p.Gly78Arg (c.232G>C) is classified Uncertain significance in ALG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-04). AlphaMissense: likely benign (0.2535); Ultra-rare (popmax 0.0503%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG2 p.Gly78Arg (c.232G>C)?

ALG2 p.Gly78Arg (c.232G>C) is associated with Inborn genetic diseases, ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Gly78Arg (c.232G>C) in the general population?

ALG2 p.Gly78Arg (c.232G>C) is ultra-rare (popmax 0.0503%, afr) (gnomAD).

What do computational predictors say about ALG2 p.Gly78Arg (c.232G>C)?

AlphaMissense predicts likely benign (score 0.2535) — an in-silico prediction, not a clinical call.

ALG2 p.Gly78Arg

c.232G>C · rs1054683823 · VCV657644

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2535 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0503%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2535	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -0.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	phastCons 0.098
Regional constraint	o/e 1.09	unconstrained · MANE · 3,957 bp · p 0.038 · regional, not allelic
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0503% African / African-American · 37/73,504 alleles

Filtering AF 0.0375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.00258% 40/1,549,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0503%	1,987
Remaining individualsnot grpmax-eligible	0.00332%	30,148
European (non-Finnish)	8.68e-05%	1,151,680

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.Gly78Arg
Coding: c.232G>C
MANE Select: NM_033087
dbSNP: rs1054683823
Type: single nucleotide variant
Location: chr9:99221663 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG2-congenital disorder of glycosylation congenital myasthenic syndrome 14

Similar variants

ALG2 p.Gly78Asp 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-gly78arg (accessed [today's date]).

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