Is AGRN p.Phe1847= (c.5541C>T) pathogenic?

AGRN p.Phe1847= (c.5541C>T) is classified Likely benign in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-19). Ultra-rare (popmax 0.0329%, mid); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Phe1847= (c.5541C>T)?

AGRN p.Phe1847= (c.5541C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Phe1847= (c.5541C>T) in the general population?

AGRN p.Phe1847= (c.5541C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

AGRN p.Phe1847=

c.5541C>T · rs1347065689 · VCV2962753

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.099	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.4, phastCons 1
Overall
CADD	4.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000248% 4/1,610,592 alleles · ultra-rare exomes 3/1,458,374 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
Remaining individualsnot grpmax-eligible	0.0016%	62,342
European (non-Finnish)	8.49e-05%	1,178,488

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.Phe1847=
Coding: c.5541C>T
MANE Select: NM_198576
dbSNP: rs1347065689
Type: single nucleotide variant
Location: chr1:1051623 (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-phe1847 (accessed [today's date]).

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