TCTN2 p.Val91=
c.273G>A · rs375065995 · VCV1630997
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -3.9 | GERP 0.24 |
| Overall | ||
| CADD | 1.415 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,924 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00031%
5/1,614,096 alleles · very rare
exomes 0/1,461,886 · genomes 5/152,210 · joint denominator
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.Val91=
- Coding
- c.273G>A
- MANE Select
- NM_024809
- dbSNP
- rs375065995
- Type
- single nucleotide variant
- Location
- chr12:123673620 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.71
Similar variants
- TCTN2 p.Val91Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-val91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown