CRIPTO c.223+43T>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 16.5%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +43 | near-intronic (+43 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -2.9 |
| Non-coding constraint | Z 2.11 | 1 kb window · o/e 0.86 · regional · uncalibrated |
| Overall | ||
| CADD | 0.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
16.5%
East Asian · 7,404/44,872 alleles
Filtering AF
16.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 16.1%
Overall
4.01%
64,747/1,613,826 alleles · common
exomes 59,496/1,461,582 · genomes 5,251/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 16.5% | 6 |
| South Asian | 14.3% | 7 |
| Middle Eastern | 8.26% | 12 |
| Amishnot grpmax-eligible | 7.13% | 14 |
| Admixed American | 5.45% | 18 |
| Remaining individualsnot grpmax-eligible | 4.63% | 22 |
| Finnishnot grpmax-eligible | 3.91% | 26 |
| Ashkenazi Jewishnot grpmax-eligible | 3.27% | 31 |
| European (non-Finnish) | 2.85% | 35 |
| African / African-American | 0.661% | 151 |
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
- CRIPTO
- Coding
- c.223+43T>A
- MANE Select
- NM_003212
- dbSNP
- rs2293023
- Type
- single nucleotide variant
- Location
- chr3:46579409 (GRCh38)
- Structure
- AlphaFold pLDDT 67.47
Similar variants
- CRIPTO c.339-8A>G Benign ★★ same type
- CRIPTO p.Arg111Gly Benign ★★ same type
- CRIPTO p.Gly151= Benign/Likely benign ★★ same type
- CRIPTO p.Arg111His Uncertain significance ★ ⚠ same type
- CRIPTO p.Arg171His Uncertain significance ★ ⚠ same type
- CRIPTO p.Arg38Cys Uncertain significance ★ ⚠ same type
- CRIPTO p.Arg38His Uncertain significance ★ ⚠ same type
- CRIPTO p.Arg60Gln 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/cripto-c-223-plus-43t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown