CRKL p.Ser12=
c.36C>T · rs150673692 · VCV785680
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.13%, afr)
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 -1.5 | GERP -4.3 |
| Overall | ||
| CADD | 5.721 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.13%
African / African-American · 845/75,066 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.04%
Overall
0.0577%
932/1,614,134 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.13% | 89 |
| Middle Eastern | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| Admixed American | 0.0483% | 2,069 |
| European (non-Finnish) | 0.00102% | 98,336 |
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
- CRKL
- Protein
- p.Ser12=
- Coding
- c.36C>T
- MANE Select
- NM_005207
- dbSNP
- rs150673692
- Type
- single nucleotide variant
- Location
- chr22:20917970 (GRCh38)
- Gene constraint
- LOEUF 0.316 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.65 · 6 PDB
- Residue 12
- an α-helix
Similar variants
- CRKL p.Ala226Val Uncertain significance ★★ ⚠ same type
- CRKL p.Arg169Gln Uncertain significance ★★ ⚠ same type
- CRKL p.Asn137Ser Uncertain significance ★★ ⚠ same type
- CRKL p.Ile263Thr Uncertain significance ★★ ⚠ same type
- CRKL p.Val178Ile Uncertain significance ★★ ⚠ same type
- CRKL c.311+12C>T Likely benign ★★ same type
- CRKL p.Gly221Ser Benign ★★ same type
- CRKL p.Val178= 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/crkl-p-ser12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown