Is AGRN p.Ser1072= (c.3216C>T) pathogenic?

AGRN p.Ser1072= (c.3216C>T) is classified Likely benign in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Very rare (popmax 0.00564%, sas); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Ser1072= (c.3216C>T)?

AGRN p.Ser1072= (c.3216C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Ser1072= (c.3216C>T) in the general population?

AGRN p.Ser1072= (c.3216C>T) is very rare (popmax 0.00564%, sas) (gnomAD).

AGRN p.Ser1072=

c.3216C>T · VCV4728525

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00564%, sas)

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.2	GERP -2.6
Overall
CADD	5.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00564% South Asian · 5/88,632 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00185%

Overall 0.00285% 45/1,581,614 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00564%	17,726
Admixed American	0.00509%	19,663
European (non-Finnish)	0.00291%	34,394
East Asian	0.00224%	44,564
Remaining individualsnot grpmax-eligible	0.00162%	61,560
African / African-American	0.00134%	74,644

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.Ser1072=
Coding: c.3216C>T
MANE Select: NM_198576
Type: single nucleotide variant
Location: chr1:1046701 (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 1072: the 'disordered' region

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-ser1072 (accessed [today's date]).

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