TTLL5 p.Pro990=
c.2970C>G · rs140291071 · VCV1164983
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.836%, eas)
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 1.4 | GERP -2.9, phastCons 1 |
| Overall | ||
| CADD | 10.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.836%
East Asian · 375/44,880 alleles
Filtering AF
0.766%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.738%
Overall
0.0324%
522/1,613,498 alleles · rare
exomes 481/1,461,180 · genomes 41/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.836% | 120 |
| Middle Eastern | 0.0331% | 3,025 |
| South Asian | 0.022% | 4,552 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,916 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| European (non-Finnish) | 0.00924% | 10,821 |
| Admixed American | 0.00167% | 60,018 |
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
- TTLL5
- Protein
- p.Pro990=
- Coding
- c.2970C>G
- MANE Select
- NM_015072
- dbSNP
- rs140291071
- Type
- single nucleotide variant
- Location
- chr14:75783514 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.56 · 1 PDB
Similar variants
- TTLL5 p.Pro990Ala Uncertain significance ★ ⚠ same residue
- TTLL5 c.1488-1G>T Likely pathogenic ★★ same type
- TTLL5 c.182-1G>T Likely pathogenic ★★ same type
- TTLL5 c.2388-2A>G Likely pathogenic ★★ same type
- TTLL5 c.3172-2A>G Likely pathogenic ★★ same type
- TTLL5 c.741-1G>A Pathogenic/Likely pathogenic ★★ same type
- TTLL5 p.Arg1170Ter Pathogenic/Likely pathogenic ★★ same type
- TTLL5 p.Arg420Ter Pathogenic/Likely pathogenic ★★ 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/ttll5-p-pro990 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown