CTNND2 p.Pro226=
c.678G>T · rs532031508 · VCV1274360
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.77%, sas)
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 -0.066 | GERP -0.43, phastCons 0.72 |
| Overall | ||
| CADD | 12.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.77%
South Asian · 385/21,700 alleles
Filtering AF
1.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.57%
Overall
0.0442%
433/979,604 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.77% | 56 |
| Remaining individualsnot grpmax-eligible | 0.123% | 811 |
| Middle Eastern | 0.102% | 982 |
| East Asian | 0.0409% | 2,444 |
| Admixed American | 0.00609% | 16,412 |
| African / African-American | 0.00177% | 56,342 |
| European (non-Finnish) | 0.000365% | 274,183 |
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
- CTNND2
- Protein
- p.Pro226=
- Coding
- c.678G>T
- MANE Select
- NM_001332
- dbSNP
- rs532031508
- Type
- single nucleotide variant
- Location
- chr5:11385164 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.88
- Residue 226
- the 'disordered' region
Similar variants
- CTNND2 p.Pro226del Likely benign ★★ same residue
- CTNND2 p.Pro226dup Benign/Likely benign ★★ same residue
- CTNND2 p.Asp700Gly Uncertain significance ★★ ⚠ same type
- CTNND2 p.Asp802Asn Uncertain significance ★★ same type
- CTNND2 p.Glu217Asp Uncertain significance ★★ ⚠ same type
- CTNND2 c.1178-153T>C Likely benign ★★ same type
- CTNND2 c.1178-164G>A Benign ★★ same type
- CTNND2 c.1372+105T>C Likely benign ★★ 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/ctnnd2-p-pro226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown