TRRAP p.Ala3214=
c.9642C>T · rs140969926 · VCV756194
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.2 | GERP -3.5 |
| Overall | ||
| CADD | 2.165 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,078 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00217%
35/1,613,990 alleles · ultra-rare
exomes 27/1,461,714 · genomes 8/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,692 |
| African / African-American | 0.00666% | 15,009 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Admixed American | 0.00333% | 30,010 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| European (non-Finnish) | 0.000763% | 131,098 |
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.Ala3214=
- Coding
- c.9642C>T
- MANE Select
- NM_001375524
- dbSNP
- rs140969926
- Type
- single nucleotide variant
- Location
- chr7:98990505 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 3214
- the fat 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-ala3214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown