TTC8 p.Val46=
c.138G>C · VCV4922812
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 1.8 | GERP -0.32, phastCons 1 |
| Overall | ||
| CADD | 7.815 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,972 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000558%
9/1,613,344 alleles · very rare
exomes 8/1,461,208 · genomes 1/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,972 |
| European (non-Finnish) | 0.000678% | 147,450 |
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
- TTC8
- Protein
- p.Val46=
- Coding
- c.138G>C
- MANE Select
- NM_144596
- Type
- single nucleotide variant
- Location
- chr14:88833716 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.48
- Residue 46
- a UniProt-annotated variant site (in rp51)
Similar variants
- TTC8 c.114+2T>C Pathogenic/Likely pathogenic ★★ same type
- TTC8 c.265+1G>A Pathogenic/Likely pathogenic ★★ same type
- TTC8 c.799-2A>G Likely pathogenic ★★ same type
- TTC8 p.Gln187Ter Pathogenic/Likely pathogenic ★★ same type
- TTC8 p.Gln247Ter Pathogenic/Likely pathogenic ★★ same type
- TTC8 p.Gln86Ter Pathogenic ★★ same type
- TTC8 p.Thr163= Pathogenic/Likely pathogenic ★★ same type
- TTC8 p.Trp226Ter 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/ttc8-p-val46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown