TTLL12 p.Pro381=
c.1143C>T · rs141200040 · VCV727507
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.829%, afr)
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 -6.3 | GERP -3.1 |
| Overall | ||
| CADD | 2.019 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.829%
African / African-American · 622/75,018 alleles
Filtering AF
0.775%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.754%
Overall
0.0438%
706/1,610,994 alleles · rare
exomes 365/1,458,698 · genomes 341/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.829% | 121 |
| Middle Eastern | 0.116% | 865 |
| Remaining individualsnot grpmax-eligible | 0.0625% | 1,601 |
| Admixed American | 0.0368% | 2,719 |
| South Asian | 0.00659% | 15,165 |
| European (non-Finnish) | 0.000848% | 117,943 |
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
- TTLL12
- Protein
- p.Pro381=
- Coding
- c.1143C>T
- MANE Select
- NM_015140
- dbSNP
- rs141200040
- Type
- single nucleotide variant
- Location
- chr22:43174295 (GRCh38)
- Gene constraint
- LOEUF 1.285 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.19
- Residue 381
- the ttl domain
Similar variants
- TTLL12 c.1645-5C>A Benign ★★ same type
- TTLL12 p.Arg84= Benign ★★ same type
- TTLL12 p.Val583= Benign ★★ same type
- TTLL12 p.Ala123Thr Uncertain significance ★ same type
- TTLL12 p.Ala146Thr Uncertain significance ★ ⚠ same type
- TTLL12 p.Ala204Val Uncertain significance ★ ⚠ same type
- TTLL12 p.Ala25Val Uncertain significance ★ ⚠ same type
- TTLL12 p.Ala281Thr 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/ttll12-p-pro381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown