AGRN p.Ala2Asp
c.5C>A · rs776698665 · VCV474165
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.254%, afr)
Conditions
1
congenital myasthenic syndrome 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.165 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP 0.38, phastCons 0.42 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic |
| Overall | ||
| CADD | 19.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.254%
African / African-American · 164/64,648 alleles
Filtering AF
0.222%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.21%
Overall
0.0157%
210/1,334,040 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.254% | 394 |
| Admixed American | 0.0844% | 1,185 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,606 |
| Middle Eastern | 0.0282% | 3,540 |
| European (non-Finnish) | 9.58e-05% | 1,043,528 |
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.Ala2Asp
- Coding
- c.5C>A
- MANE Select
- NM_198576
- dbSNP
- rs776698665
- Type
- single nucleotide variant
- Location
- chr1:1020177 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 69.79 · 1 PDB
Similar variants
- AGRN p.Ala2Pro Uncertain significance ★ 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
- AGRN c.1384+6C>T 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-ala2asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown