TRRAP p.Val3758=
c.11274C>T · rs777339560 · VCV1577942
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0072%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.123 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -1.8, phastCons 0.25 |
| Overall | ||
| CADD | 1.345 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0072%
European (non-Finnish) · 85/1,180,058 alleles
Filtering AF
0.00596%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00558%
90/1,614,162 alleles · very rare
exomes 81/1,461,892 · genomes 9/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0072% | 13,883 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
| Finnishnot grpmax-eligible | 0.00156% | 64,042 |
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.Val3758=
- Coding
- c.11274C>T
- MANE Select
- NM_001375524
- dbSNP
- rs777339560
- Type
- single nucleotide variant
- Location
- chr7:99011472 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 3758
- the pi3k/pi4k catalytic domain; an α-helix
Similar variants
- 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
- TRRAP c.8247+5G>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/trrap-p-val3758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown