CRIPTO c.88+8A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.05%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | Δ0.27 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.55, phastCons 0.025 |
| Non-coding constraint | Z 2.11 | 1 kb window · o/e 0.86 · regional · uncalibrated |
| Overall | ||
| CADD | 3.345 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.05%
Admixed American · 30/60,008 alleles
Filtering AF
0.0359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0312%
Overall
0.00378%
61/1,613,984 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.05% | 2,000 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| African / African-American | 0.004% | 24,985 |
| European (non-Finnish) | 0.00169% | 59,001 |
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.88+8A>G
- MANE Select
- NM_003212
- dbSNP
- rs538573047
- Type
- single nucleotide variant
- Location
- chr3:46579155 (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-88-plus-8a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown