Is AGRN p.Arg305fs (c.914_947del) pathogenic?

AGRN p.Arg305fs (c.914947del) is classified Pathogenic in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-08). Absent from gnomAD; Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Arg305fs (c.914_947del)?

AGRN p.Arg305fs (c.914_947del) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Arg305fs (c.914_947del) in the general population?

AGRN p.Arg305fs (c.914_947del) is absent from gnomAD (gnomAD).

AGRN p.Arg305fs

c.914_947del · rs1557700705 · VCV574478

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 36
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.4	GERP -2.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg305fs
Coding: c.914_947del
MANE Select: NM_198576
dbSNP: rs1557700705
Type: Deletion
Location: chr1:1041355 (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 305: 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.Arg305= Likely benign ★ same residue
AGRN c.1177+4_1177+50del Pathogenic/Likely pathogenic ★★ same condition
AGRN p.Gln1406fs Pathogenic/Likely pathogenic ★★ same condition
AGRN c.1385-15_1385-14del Benign ★★ same condition
AGRN c.4106-75_4106-74del Benign ★★ same condition
AGRN c.4298+21_4298+55del Likely benign ★★ same condition
AGRN c.4298+6_4298+88del Benign/Likely benign ★★ same condition
AGRN c.3632-2del Likely pathogenic ★ 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-arg305fs (accessed [today's date]).

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