TTLL5 p.Ala331=
c.993T>C · rs2140204943 · VCV2011441
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.56 | GERP -5.6, phastCons 0.072 |
| Overall | ||
| CADD | 6.984 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,708 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,792 alleles · very rare
exomes 4/1,461,424 · genomes 0/152,368 · joint denominator
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.Ala331=
- Coding
- c.993T>C
- MANE Select
- NM_015072
- dbSNP
- rs2140204943
- Type
- single nucleotide variant
- Location
- chr14:75720654 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.56 · 1 PDB
- Residue 331
- the ttl domain
Similar variants
- TTLL5 p.Ala331Thr Uncertain significance ★ ⚠ same residue
- TTLL5 p.Ala331Val 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
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-ala331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown