Is AGRN p.Arg301= (c.903C>T) pathogenic?

AGRN p.Arg301= (c.903C>T) is classified Likely benign in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Very rare (popmax 0.0012%, sas); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Arg301= (c.903C>T)?

AGRN p.Arg301= (c.903C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Arg301= (c.903C>T) in the general population?

AGRN p.Arg301= (c.903C>T) is very rare (popmax 0.0012%, sas) (gnomAD).

AGRN p.Arg301=

c.903C>T · VCV4777862

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Conditions

congenital myasthenic syndrome 8

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 -6.9	GERP -2.3
Overall
CADD	1.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,174 alleles

Overall 0.00131% 2/152,108 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,174
European (non-Finnish)	8.74e-05%	1,144,518

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: AGRN
Protein: p.Arg301=
Coding: c.903C>T
MANE Select: NM_198576
Type: single nucleotide variant
Location: chr1:1041348 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.79 · 1 PDB
Residue 301: a disulfide bond; the kazal-like 2 domain

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 p.Arg301fs Pathogenic ★ same residue
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

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-arg301 (accessed [today's date]).

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