TTLL5 p.Arg554=
c.1662T>G · rs1045127706 · VCV1089095
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss, 12 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.045 | GERP 1.3, phastCons 0.95 |
| Overall | ||
| CADD | 9.021 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
Admixed American · 25/60,000 alleles
Filtering AF
0.0289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0247%
Overall
0.00167%
27/1,614,040 alleles · ultra-rare
exomes 8/1,461,840 · genomes 19/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0417% | 2,400 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
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.Arg554=
- Coding
- c.1662T>G
- MANE Select
- NM_015072
- dbSNP
- rs1045127706
- Type
- single nucleotide variant
- Location
- chr14:75764726 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.56 · 1 PDB
Similar variants
- TTLL5 p.Arg554Cys 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-arg554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown