Is AGRN p.Pro1834= (c.5502G>A) pathogenic?

AGRN p.Pro1834= (c.5502G>A) is classified Likely benign in AGRN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). Very rare (popmax 0.00675%, amr); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Pro1834= (c.5502G>A)?

AGRN p.Pro1834= (c.5502G>A) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Pro1834= (c.5502G>A) in the general population?

AGRN p.Pro1834= (c.5502G>A) is very rare (popmax 0.00675%, amr) (gnomAD).

AGRN p.Pro1834=

c.5502G>A · rs371302168 · VCV1126592

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00675%, amr)

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -2.8
Overall
CADD	0.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00675% Admixed American · 4/59,252 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00194% 31/1,601,236 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00675%	14,813
Remaining individualsnot grpmax-eligible	0.00485%	20,617
European (non-Finnish)	0.00205%	48,866

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.Pro1834=
Coding: c.5502G>A
MANE Select: NM_198576
dbSNP: rs371302168
Type: single nucleotide variant
Location: chr1:1051584 (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 1834: the egf-like 4 domain; a disulfide bond

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.Pro1834Leu Likely benign ★★ 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-pro1834 (accessed [today's date]).

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