CRKL p.Ala208=
c.624T>C · VCV4765029
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, mid)
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 -0.95 | GERP -0.84, phastCons 0.005 |
| Overall | ||
| CADD | 6.041 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
Middle Eastern · 4/6,062 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.000684%
10/1,461,894 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| Admixed American | 0.00167% | 60,024 |
| European (non-Finnish) | 0.000254% | 393,348 |
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.Ala208=
- Coding
- c.624T>C
- MANE Select
- NM_005207
- Type
- single nucleotide variant
- Location
- chr22:20934091 (GRCh38)
- Gene constraint
- LOEUF 0.316 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.65 · 6 PDB
- Residue 208
- an α-helix; the 'disordered' region
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.Ser12= 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-ala208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown