Is AGRN p.Pro1096Ser (c.3286C>T) pathogenic?

AGRN p.Pro1096Ser (c.3286C>T) is classified Uncertain significance in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Rare (popmax 0.123%, eas); Associated with Inborn genetic diseases.

What condition is associated with AGRN p.Pro1096Ser (c.3286C>T)?

AGRN p.Pro1096Ser (c.3286C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGRN p.Pro1096Ser (c.3286C>T) in the general population?

AGRN p.Pro1096Ser (c.3286C>T) is rare (popmax 0.123%, eas) (gnomAD).

AGRN p.Pro1096Ser

c.3286C>T · rs766445747 · VCV2217240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.123%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.116	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.1, phastCons 0.83
Regional constraint	o/e 1.02	unconstrained · MANE · 8,500 bp · p 0.41 · regional, not allelic
Overall
CADD	13.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% East Asian · 54/43,958 alleles

Filtering AF 0.0967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0872%

Overall 0.00359% 57/1,586,522 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.123%	814
Remaining individualsnot grpmax-eligible	0.00487%	20,524

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.Pro1096Ser
Coding: c.3286C>T
MANE Select: NM_198576
dbSNP: rs766445747
Type: single nucleotide variant
Location: chr1:1046855 (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 1096: the 'disordered' region

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

Similar variants

AGRN p.Pro1096= Likely benign ★ same residue
AGRN p.Ala1012Thr Uncertain significance ★★ same condition
AGRN p.Ala1056Thr Uncertain significance ★★ same condition
AGRN p.Ala1304Thr Uncertain significance ★★ same condition
AGRN p.Ala1325Gly Uncertain significance ★★ same condition
AGRN p.Ala1372Thr Uncertain significance ★★ same condition
AGRN p.Ala1737Val Uncertain significance ★★ same condition
AGRN p.Ala302Gly 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-pro1096ser (accessed [today's date]).

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