AGRN p.Pro757=
c.2271G>A · rs150123719 · VCV263170
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0347%, nfe)
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 -12 | GERP -2.3 |
| Overall | ||
| CADD | 0.037 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0347%
European (non-Finnish) · 409/1,179,938 alleles
Filtering AF
0.0319%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0307%
Overall
0.0269%
434/1,612,380 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0347% | 2,885 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,162 |
| Admixed American | 0.01% | 10,002 |
| African / African-American | 0.004% | 25,009 |
| Finnishnot grpmax-eligible | 0.00159% | 62,766 |
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.Pro757=
- Coding
- c.2271G>A
- MANE Select
- NM_198576
- dbSNP
- rs150123719
- Type
- single nucleotide variant
- Location
- chr1:1045177 (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.Pro757Arg Uncertain significance ★ same residue
- AGRN p.Pro757Gln Uncertain significance ★ same residue
- AGRN p.Pro757Leu 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
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-pro757 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown