TRIO p.Ser403=
c.1209G>A · rs189300218 · VCV715714
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.235%, amr)
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 -7.6 | GERP -4.3 |
| Overall | ||
| CADD | 2.094 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.235%
Admixed American · 141/60,014 alleles
Filtering AF
0.203%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.191%
Overall
0.00985%
159/1,613,634 alleles · rare
exomes 148/1,461,398 · genomes 11/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.235% | 426 |
| East Asian | 0.0111% | 8,971 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| European (non-Finnish) | 0.000933% | 107,237 |
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
- TRIO
- Protein
- p.Ser403=
- Coding
- c.1209G>A
- MANE Select
- NM_007118
- dbSNP
- rs189300218
- Type
- single nucleotide variant
- Location
- chr5:14297104 (GRCh38)
- Gene constraint
- LOEUF 0.217 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- TRIO c.2391+1G>A Pathogenic/Likely pathogenic ★★ same type
- TRIO c.3447+2T>C Likely pathogenic ★★ same type
- TRIO c.5497-1G>C Likely pathogenic ★★ same type
- TRIO c.6153+1G>A Pathogenic/Likely pathogenic ★★ same type
- TRIO p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same type
- TRIO p.Arg1078Trp Pathogenic/Likely pathogenic ★★ same type
- TRIO p.Arg1411Ter Pathogenic/Likely pathogenic ★★ same type
- TRIO p.Arg1428Gln Pathogenic/Likely pathogenic ★★ 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/trio-p-ser403 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown