TRRAP p.Thr646=
c.1938G>A · rs782311635 · VCV1980519
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.093 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.8 |
| Overall | ||
| CADD | 2.093 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
Admixed American · 15/59,982 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.00248%
40/1,614,022 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.025% | 3,999 |
| East Asian | 0.00445% | 22,450 |
| South Asian | 0.0022% | 45,543 |
| European (non-Finnish) | 0.00169% | 59,001 |
| African / African-American | 0.00133% | 74,932 |
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.Thr646=
- Coding
- c.1938G>A
- MANE Select
- NM_001375524
- dbSNP
- rs782311635
- Type
- single nucleotide variant
- Location
- chr7:98911202 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 646
- an α-helix
Similar variants
- TRRAP p.Thr646Met 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-thr646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown