Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -2.4, phastCons 0.94 |
| Overall | ||
| CADD | 6.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,859/44,878 alleles
Filtering AF
99.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 98.9%
Overall
90.7%
1,462,644/1,612,940 alleles · common
exomes 1,337,920/1,460,682 · genomes 124,724/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| Amishnot grpmax-eligible | 98.6% | 1 |
| South Asian | 95.2% | 1 |
| Finnishnot grpmax-eligible | 95.2% | 1 |
| Admixed American | 92.3% | 1 |
| European (non-Finnish) | 92.1% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 92% | 1 |
| Remaining individualsnot grpmax-eligible | 89.9% | 1 |
| Middle Eastern | 86.5% | 1 |
| African / African-American | 52.8% | 2 |
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.Phe1186=
- Coding
- c.3558T>C
- MANE Select
- NM_198576
- dbSNP
- rs10267
- Type
- single nucleotide variant
- Location
- chr1:1047614 (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 1186
- the sea domain
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-phe1186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown