GSN p.Pro408=
c.1224C>T · rs780270307 · VCV2071556
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0657%, mid)
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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.055 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0657%
Middle Eastern · 4/6,084 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00527%
85/1,613,734 alleles · ultra-rare
exomes 83/1,461,534 · genomes 2/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0657% | 1,521 |
| South Asian | 0.0439% | 2,277 |
| East Asian | 0.00445% | 22,449 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,235 |
| European (non-Finnish) | 0.00305% | 32,771 |
| Admixed American | 0.00167% | 60,012 |
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
- GSN
- Protein
- p.Pro408=
- Coding
- c.1224C>T
- MANE Select
- NM_198252
- dbSNP
- rs780270307
- Type
- single nucleotide variant
- Location
- chr9:121321300 (GRCh38)
- Gene constraint
- LOEUF 0.788 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.76 · 65 PDB
Similar variants
- GSN p.Asn160Lys Pathogenic ★★ same type
- GSN p.Asp163Asn Pathogenic/Likely pathogenic ★★ same type
- GSN p.Asp163Tyr Pathogenic/Likely pathogenic ★★ same type
- GSN c.1762+2T>C Uncertain significance ★★ same type
- GSN c.513+1G>A Uncertain significance ★★ same type
- GSN c.753+1G>A Uncertain significance ★★ same type
- GSN c.754-1G>T Uncertain significance ★★ same type
- GSN c.-9-1981C>T 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/gsn-p-pro408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown