TCTN2 p.Pro69=
c.207G>A · rs775096865 · VCV1649134
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00441%, nfe)
Conditions
2
Meckel 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 -14 | GERP -2.9 |
| Overall | ||
| CADD | 0.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00441%
European (non-Finnish) · 52/1,180,008 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.00335%
54/1,614,012 alleles · very rare
exomes 52/1,461,852 · genomes 2/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00441% | 22,692 |
| East Asian | 0.00223% | 44,894 |
| African / African-American | 0.00133% | 74,920 |
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.Pro69=
- Coding
- c.207G>A
- MANE Select
- NM_024809
- dbSNP
- rs775096865
- Type
- single nucleotide variant
- Location
- chr12:123672072 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.71
Similar variants
- TCTN2 p.Pro69Leu Uncertain significance ★ ⚠ 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-pro69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown