Is AGRN p.Phe1784= (c.5352C>T) pathogenic?

AGRN p.Phe1784= (c.5352C>T) is classified Benign/Likely benign in AGRN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.61%, afr); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Phe1784= (c.5352C>T)?

AGRN p.Phe1784= (c.5352C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Phe1784= (c.5352C>T) in the general population?

AGRN p.Phe1784= (c.5352C>T) is low-frequency (popmax 1.61%, afr) (gnomAD).

AGRN p.Phe1784=

c.5352C>T · rs112073270 · VCV263197

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.61%, afr)

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 -4.6	GERP -2.9
Overall
CADD	0.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.61% African / African-American · 1,200/74,316 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.0927% 1,453/1,566,626 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.61%	62
Remaining individualsnot grpmax-eligible	0.104%	965
Admixed American	0.0964%	1,037
Middle Eastern	0.0176%	5,682
European (non-Finnish)	0.011%	9,109
South Asian	0.00937%	10,672
Finnishnot grpmax-eligible	0.00344%	29,099
East Asian	0.00233%	42,922

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.Phe1784=
Coding: c.5352C>T
MANE Select: NM_198576
dbSNP: rs112073270
Type: single nucleotide variant
Location: chr1:1051351 (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 1784: the laminin g-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 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-phe1784 (accessed [today's date]).

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