AGRN p.Thr863=
c.2589G>A · rs776485359 · VCV263174
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.3 |
| Overall | ||
| CADD | 0.733 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,179,966 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00291%
47/1,613,216 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,441 |
| South Asian | 0.00329% | 30,365 |
| African / African-American | 0.00133% | 74,924 |
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.Thr863=
- Coding
- c.2589G>A
- MANE Select
- NM_198576
- dbSNP
- rs776485359
- Type
- single nucleotide variant
- Location
- chr1:1045785 (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 863
- the laminin egf-like 2 domain; a disulfide bond
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-thr863 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown