TTI2 p.Leu241=
c.723G>A · rs114120191 · VCV768234
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.19 | GERP -1.8, phastCons 0.94 |
| Overall | ||
| CADD | 7.831 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.23%
African / African-American · 3,920/74,930 alleles
Filtering AF
5.09%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.04%
Overall
0.28%
4,524/1,613,844 alleles · common
exomes 2,184/1,461,856 · genomes 2,340/151,988 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.23% | 19 |
| Admixed American | 0.434% | 231 |
| Remaining individualsnot grpmax-eligible | 0.35% | 285 |
| Middle Eastern | 0.297% | 336 |
| South Asian | 0.011% | 9,108 |
| European (non-Finnish) | 0.00814% | 12,291 |
| East Asian | 0.00223% | 44,864 |
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
- TTI2
- Protein
- p.Leu241=
- Coding
- c.723G>A
- MANE Select
- NM_001102401
- dbSNP
- rs114120191
- Type
- single nucleotide variant
- Location
- chr8:33509857 (GRCh38)
- Gene constraint
- LOEUF 0.758 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.85 · 2 PDB
Similar variants
- TTI2 p.Arg334Gln Uncertain significance ★★ ⚠ same type
- TTI2 p.Arg355His Uncertain significance ★★ ⚠ same type
- TTI2 p.Arg379Trp Uncertain significance ★★ ⚠ same type
- TTI2 p.Gly190Val Uncertain significance ★★ ⚠ same type
- TTI2 p.Pro149Leu Uncertain significance ★★ ⚠ same type
- TTI2 p.Thr232Ile Uncertain significance ★★ ⚠ same type
- TTI2 p.Thr237Ala Uncertain significance ★★ ⚠ same type
- TTI2 c.-99-31C>T Benign ★★ 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/tti2-p-leu241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown