AGRN p.Arg4Pro
c.11G>C · rs539283387 · VCV387476
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.22%, 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 | 0.13 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.21 | GERP -0.77, phastCons 0.22 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic |
| Overall | ||
| CADD | 11.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.22%
African / African-American · 2,728/64,630 alleles
Filtering AF
4.09%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.04%
Overall
0.224%
2,982/1,333,304 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.22% | 24 |
| Admixed American | 0.297% | 336 |
| Remaining individualsnot grpmax-eligible | 0.232% | 431 |
| Middle Eastern | 0.198% | 504 |
| European (non-Finnish) | 0.0044% | 22,729 |
| South Asian | 0.0038% | 26,338 |
| East Asian | 0.00328% | 30,520 |
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.Arg4Pro
- Coding
- c.11G>C
- MANE Select
- NM_198576
- dbSNP
- rs539283387
- Type
- single nucleotide variant
- Location
- chr1:1020183 (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.Arg4Trp Uncertain significance ★ same residue
- AGRN p.Arg4Gly 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
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-arg4pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown