TRRAP p.Ala322=
c.966A>G · rs370423667 · VCV1942696
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -3.1 |
| Overall | ||
| CADD | 2.845 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/75,060 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.000681%
11/1,614,246 alleles · ultra-rare
exomes 2/1,461,888 · genomes 9/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,506 |
| European (non-Finnish) | 8.47e-05% | 1,180,054 |
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
- TRRAP
- Protein
- p.Ala322=
- Coding
- c.966A>G
- MANE Select
- NM_001375524
- dbSNP
- rs370423667
- Type
- single nucleotide variant
- Location
- chr7:98903447 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 322
- an α-helix
Similar variants
- TRRAP p.Ala322Ser Uncertain significance ★★ ⚠ same residue
- TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
- TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Val1030Ile Likely pathogenic ★★ same type
- TRRAP c.2622+3A>G Uncertain significance ★★ same type
- TRRAP c.7176+4A>G 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/trrap-p-ala322 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown