CRIPTO c.448+243G>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 15.7%, 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 +243 | deep intronic (+243 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -0.32, phastCons 0.033 |
| Non-coding constraint | Z 1.28 | 1 kb window · o/e 0.91 · regional · uncalibrated |
| Overall | ||
| CADD | 7.446 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15.7%
East Asian · 812/5,180 alleles
Filtering AF
14.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.4%
Overall
3.52%
5,360/152,256 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 15.7% | 6 |
| South Asian | 14.9% | 7 |
| Middle Eastern | 8.84% | 11 |
| Amishnot grpmax-eligible | 7.13% | 14 |
| Admixed American | 5.18% | 19 |
| Remaining individualsnot grpmax-eligible | 4.16% | 24 |
| Finnishnot grpmax-eligible | 3.88% | 26 |
| Ashkenazi Jewishnot grpmax-eligible | 3.4% | 29 |
| European (non-Finnish) | 2.82% | 35 |
| African / African-American | 0.982% | 102 |
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.448+243G>A
- MANE Select
- NM_003212
- dbSNP
- rs2280413
- Type
- single nucleotide variant
- Location
- chr3:46580303 (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-448-plus-243g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown