CCT2 p.Ala523=
c.1569G>A · rs61754224 · VCV1082495
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0555%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -4, phastCons 0.99 |
| Overall | ||
| CADD | 10.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0555%
Admixed American · 33/59,498 alleles
Filtering AF
0.0406%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0354%
Overall
0.0279%
450/1,610,764 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0555% | 1,803 |
| Remaining individualsnot grpmax-eligible | 0.0353% | 2,834 |
| European (non-Finnish) | 0.0327% | 3,061 |
| African / African-American | 0.0134% | 7,490 |
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
- Protein
- p.Ala523=
- Coding
- c.1569G>A
- MANE Select
- NM_006431
- dbSNP
- rs61754224
- Type
- single nucleotide variant
- Location
- chr12:69599996 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.85 · 71 PDB
- Residue 523
- an α-helix
Similar variants
- CCT2 p.Ala523Gly Uncertain significance ★ ⚠ same residue
- 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
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-p-ala523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown