CCT2 c.446+6T>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00111%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +6 | donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.55 | donor loss · deltas |
| Pangolin | Δ0.67 | loss · gain 0.16 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00111%
South Asian · 1/90,322 alleles
Overall
7.01e-05%
1/1,425,902 alleles · very rare
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
- CCT2
- Coding
- c.446+6T>C
- MANE Select
- NM_006431
- Type
- single nucleotide variant
- Location
- chr12:69588268 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.85 · 71 PDB
Similar variants
- CCT2 p.Ala128Thr Uncertain significance ★★ ⚠ same type
- CCT2 p.Ala133Val Uncertain significance ★★ ⚠ same type
- CCT2 p.Ala145Val Uncertain significance ★★ ⚠ same type
- CCT2 p.Arg156Cys Uncertain significance ★★ ⚠ same type
- CCT2 p.Arg255Gln Uncertain significance ★★ ⚠ same type
- CCT2 p.Arg255Trp Uncertain significance ★★ ⚠ same type
- CCT2 p.Arg281Cys Uncertain significance ★★ ⚠ same type
- CCT2 p.Arg281His Uncertain significance ★★ ⚠ same type
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/cct2-c-446-plus-6t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown