TCTN2 p.Phe234Ser
c.701T>C · VCV3574344
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4818 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Meckel syndrome, type 8
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4818 | ambiguous |
|---|---|---|
| REVEL | 0.555 | indeterminate |
| SaProt | LLR -4.63 | tolerated |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.9, phastCons 0.92 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 36 kb · p 0.029 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TCTN2
- Protein
- p.Phe234Ser
- Coding
- c.701T>C
- MANE Select
- NM_024809
- Type
- single nucleotide variant
- Location
- chr12:123686972 (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.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
- TCTN2 p.Gln306Ter 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-phe234ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown