Is AGRN p.Arg385= (c.1155C>T) pathogenic?

AGRN p.Arg385= (c.1155C>T) is classified Likely benign in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-07). Very rare (popmax 0.00425%, nfe); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Arg385= (c.1155C>T)?

AGRN p.Arg385= (c.1155C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Arg385= (c.1155C>T) in the general population?

AGRN p.Arg385= (c.1155C>T) is very rare (popmax 0.00425%, nfe) (gnomAD).

AGRN p.Arg385=

c.1155C>T · rs373114285 · VCV1554704

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00425%, nfe)

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 0.51	GERP 0.3, phastCons 1
Overall
CADD	12.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00425% European (non-Finnish) · 50/1,177,104 alleles

Filtering AF 0.00327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0033% 53/1,608,036 alleles · very rare exomes 49/1,456,252 · genomes 4/151,784 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00425%	23,542
Remaining individualsnot grpmax-eligible	0.00321%	31,113
South Asian	0.0011%	90,886

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.Arg385=
Coding: c.1155C>T
MANE Select: NM_198576
dbSNP: rs373114285
Type: single nucleotide variant
Location: chr1:1041680 (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 385: the kazal-like 3 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.Arg385Cys Uncertain significance ★ 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-arg385 (accessed [today's date]).

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