TTC8 p.Val447Ala
c.1340T>C · rs775992377 · VCV2153993
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0245%, eas)
Conditions
4
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.073 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.67, phastCons 0.38 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic |
| Overall | ||
| CADD | 18.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0245%
East Asian · 11/44,870 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.000868%
14/1,613,674 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0245% | 4,079 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,226 |
| European (non-Finnish) | 8.48e-05% | 1,179,810 |
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.Val447Ala
- Coding
- c.1340T>C
- MANE Select
- NM_144596
- dbSNP
- rs775992377
- Type
- single nucleotide variant
- Location
- chr14:88872445 (GRCh38)
- Gene constraint
- LOEUF 0.8 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.48
Similar variants
- TTC8 p.Val447Ile Uncertain significance ★ same residue
- TTC8 c.114+2T>C Pathogenic/Likely pathogenic ★★ same condition
- TTC8 c.265+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TTC8 c.799-2A>G Likely pathogenic ★★ same condition
- TTC8 p.Gln187Ter Pathogenic/Likely pathogenic ★★ same condition
- TTC8 p.Gln247Ter Pathogenic/Likely pathogenic ★★ same condition
- TTC8 p.Gln86Ter Pathogenic ★★ same condition
- TTC8 p.Thr163= Pathogenic/Likely pathogenic ★★ same condition
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-val447ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown