TCTN2 p.Pro170=
c.510T>C · rs769707766 · VCV1635859
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
Conditions
2
Joubert syndrome
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 -2.4 | GERP -0.81 |
| Overall | ||
| CADD | 5.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,086 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00118%
19/1,614,028 alleles · ultra-rare
exomes 17/1,461,794 · genomes 2/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,060 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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
- TCTN2
- Protein
- p.Pro170=
- Coding
- c.510T>C
- MANE Select
- NM_024809
- dbSNP
- rs769707766
- Type
- single nucleotide variant
- Location
- chr12:123679235 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.71
Similar variants
- TCTN2 c.1506-2A>G Pathogenic/Likely pathogenic ★★ same condition
- TCTN2 c.1612+1G>A Likely pathogenic ★★ same condition
- TCTN2 c.191-2A>T Pathogenic/Likely pathogenic ★★ same condition
- TCTN2 c.267+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TCTN2 c.565-1G>A Likely pathogenic ★★ same condition
- TCTN2 c.765-1G>C Likely pathogenic ★★ same condition
- TCTN2 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
- TCTN2 p.Arg446Ter 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/tctn2-p-pro170 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown