AGRN p.Ala1506=
c.4518G>A · rs376592885 · VCV263187
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0487%, sas)
Conditions
1
congenital myasthenic syndrome 8
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 2.8 | GERP 0.028, phastCons 1 |
| Overall | ||
| CADD | 7.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0487%
South Asian · 43/88,230 alleles
Filtering AF
0.0371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0331%
Overall
0.0204%
324/1,589,854 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0487% | 2,052 |
| East Asian | 0.0297% | 3,369 |
| Finnishnot grpmax-eligible | 0.0232% | 4,308 |
| European (non-Finnish) | 0.0203% | 4,934 |
| Middle Eastern | 0.0166% | 6,030 |
| Admixed American | 0.0143% | 6,977 |
| Remaining individualsnot grpmax-eligible | 0.0114% | 8,799 |
| African / African-American | 0.00134% | 74,710 |
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.Ala1506=
- Coding
- c.4518G>A
- MANE Select
- NM_198576
- dbSNP
- rs376592885
- Type
- single nucleotide variant
- Location
- chr1:1049569 (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 1506
- the laminin g-like 1 domain
Similar variants
- AGRN p.Ala1506Val Uncertain significance ★★ same residue
- AGRN p.Ala1506Thr 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
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-ala1506 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown