Is AGRN p.Ser254Arg (c.762C>G) pathogenic?

AGRN p.Ser254Arg (c.762C>G) is classified Uncertain significance in AGRN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGRN p.Ser254Arg (c.762C>G)?

AGRN p.Ser254Arg (c.762C>G) is associated with Inborn genetic diseases, congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Ser254Arg (c.762C>G) in the general population?

AGRN p.Ser254Arg (c.762C>G) is absent from gnomAD v4.1 (gnomAD).

AGRN p.Ser254Arg

c.762C>G · rs1208459024 · VCV2042499

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,469,488)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.374	indeterminate
Splicing
SpliceAI	Δ0.44	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.52	GERP -1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,469,488). 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.Ser254Arg
Coding: c.762C>G
MANE Select: NM_198576
dbSNP: rs1208459024
Type: single nucleotide variant
Location: chr1:1041207 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 8

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-ser254arg (accessed [today's date]).

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