Is AGRN p.Arg245= (c.733C>A) pathogenic?

AGRN p.Arg245= (c.733C>A) is classified Likely benign in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). No allele count reported in gnomAD v4.1 (AN 1,420,052); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Arg245= (c.733C>A)?

AGRN p.Arg245= (c.733C>A) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Arg245= (c.733C>A) in the general population?

AGRN p.Arg245= (c.733C>A) is no allele count reported in gnomAD v4.1 (AN 1,420,052) (gnomAD).

AGRN p.Arg245=

c.733C>A · rs750017108 · VCV1101680

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,420,052)

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP -1.4, phastCons 1
Overall
CADD	9.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,420,052). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGRN
Protein: p.Arg245=
Coding: c.733C>A
MANE Select: NM_198576
dbSNP: rs750017108
Type: single nucleotide variant
Location: chr1:1041178 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.79 · 1 PDB

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

Disease context

congenital myasthenic syndrome 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGRN c.3632-1G>C Likely pathogenic ★★ same condition
AGRN p.Arg1671Ter Pathogenic/Likely pathogenic ★★ same condition
AGRN p.Arg834Ter Pathogenic/Likely pathogenic ★★ same condition
AGRN p.Gly1582Arg Pathogenic ★★ same condition
AGRN p.Gly1675Ser Pathogenic/Likely pathogenic ★★ same condition
AGRN c.1177+4A>G Uncertain significance ★★ same condition
AGRN c.1384+6C>T Uncertain significance ★★ same condition
AGRN c.4879+4G>A 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/agrn-p-arg245 (accessed [today's date]).

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