AGRN p.Asp99=
c.297C>T · rs771686237 · VCV736899
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0245%, eas)
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 -0.54 | GERP -0.049, phastCons 0.028 |
| Overall | ||
| CADD | 8.561 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0245%
East Asian · 11/44,892 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00093%
15/1,613,200 alleles · ultra-rare
exomes 14/1,461,012 · genomes 1/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0245% | 4,081 |
| South Asian | 0.00329% | 30,361 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
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.Asp99=
- Coding
- c.297C>T
- MANE Select
- NM_198576
- dbSNP
- rs771686237
- Type
- single nucleotide variant
- Location
- chr1:1022296 (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 99
- the nta domain
Similar variants
- AGRN c.3632-1G>C Likely pathogenic ★★ same type
- AGRN p.Arg1671Ter Pathogenic/Likely pathogenic ★★ same type
- AGRN p.Arg834Ter Pathogenic/Likely pathogenic ★★ same type
- AGRN p.Gly1582Arg Pathogenic ★★ same type
- AGRN p.Gly1675Ser Pathogenic/Likely pathogenic ★★ same type
- AGRN c.1177+4A>G Uncertain significance ★★ same type
- AGRN c.1384+6C>T Uncertain significance ★★ same type
- AGRN c.4879+4G>A Uncertain significance ★★ same type
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-asp99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown