TRAPPC9 p.Ala421=
c.1263G>A · rs113690180 · VCV437034
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.105%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.1 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.599 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.105%
Admixed American · 63/60,032 alleles
Filtering AF
0.0841%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0766%
Overall
0.00558%
90/1,614,240 alleles · rare
exomes 82/1,461,878 · genomes 8/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.105% | 953 |
| African / African-American | 0.00932% | 10,724 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| East Asian | 0.00223% | 44,890 |
| European (non-Finnish) | 0.0011% | 90,771 |
| South Asian | 0.0011% | 91,090 |
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
- TRAPPC9
- Protein
- p.Ala421=
- Coding
- c.1263G>A
- MANE Select
- NM_001160372
- dbSNP
- rs113690180
- Type
- single nucleotide variant
- Location
- chr8:140371052 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.98
Similar variants
- TRAPPC9 p.Ala421Val Uncertain significance ★★ ⚠ same residue
- TRAPPC9 p.Arg472Ter Pathogenic/Likely pathogenic ★★ same condition
- TRAPPC9 p.Glu123Ter Pathogenic ★★ same condition
- TRAPPC9 p.Glu97Ter Pathogenic ★★ same condition
- TRAPPC9 c.-212G>C Uncertain significance ★★ same condition
- TRAPPC9 c.-4C>A Uncertain significance ★★ same condition
- TRAPPC9 c.-69C>T Uncertain significance ★★ same condition
- TRAPPC9 c.-74C>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/trappc9-p-ala421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown