CRIPTO p.Leu152=
c.456T>C · rs112928637 · VCV1318194
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.6%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.8 | GERP -3.6 |
| Overall | ||
| CADD | 0.167 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.6%
Middle Eastern · 218/6,056 alleles
Filtering AF
3.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.06%
Overall
2.64%
42,571/1,613,482 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.6% | 28 |
| East Asian | 3.13% | 32 |
| European (non-Finnish) | 2.95% | 34 |
| Remaining individualsnot grpmax-eligible | 2.57% | 39 |
| Admixed American | 2.11% | 47 |
| Amishnot grpmax-eligible | 2.08% | 48 |
| African / African-American | 1.62% | 62 |
| Ashkenazi Jewishnot grpmax-eligible | 1.5% | 67 |
| South Asian | 1.33% | 75 |
| Finnishnot grpmax-eligible | 0.695% | 144 |
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
- Protein
- p.Leu152=
- Coding
- c.456T>C
- MANE Select
- NM_003212
- dbSNP
- rs112928637
- Type
- single nucleotide variant
- Location
- chr3:46581139 (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-p-leu152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown