TTC8 p.Ile474Val
c.1420A>G · rs1244721977 · VCV1367817
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
3
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.3 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic |
| Overall | ||
| CADD | 0.802 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,882 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,611,150 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,882 |
| European (non-Finnish) | 0.000255% | 392,731 |
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.Ile474Val
- Coding
- c.1420A>G
- MANE Select
- NM_144596
- dbSNP
- rs1244721977
- Type
- single nucleotide variant
- Location
- chr14:88875098 (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.Ile474= Likely benign ★ 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-ile474val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown