CDKN1C p.Ala217=
c.651G>A · rs761539484 · VCV1100347
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0423%, mid)
Conditions
1
Beckwith-Wiedemann syndrome
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 0.53, phastCons 0.97 |
| Overall | ||
| CADD | 14.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0423%
Middle Eastern · 2/4,730 alleles
Filtering AF
0.00743%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.000386%
5/1,295,940 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0423% | 2,365 |
| Remaining individualsnot grpmax-eligible | 0.00186% | 53,716 |
| European (non-Finnish) | 0.000183% | 547,726 |
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
- CDKN1C
- Protein
- p.Ala217=
- Coding
- c.651G>A
- MANE Select
- NM_001122630
- dbSNP
- rs761539484
- Type
- single nucleotide variant
- Location
- chr11:2884806 (GRCh38)
- Gene constraint
- LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.93
- Residue 217
- the 'disordered' region
Similar variants
- CDKN1C p.Ala217Thr Uncertain significance ★ ⚠ same residue
- CDKN1C p.Ala217Val Uncertain significance ★ ⚠ same residue
- CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
- CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same condition
- CDKN1C p.Gln219Ter Pathogenic ★★ same condition
- CDKN1C p.Gln221Ter Pathogenic ★★ same condition
- CDKN1C p.Gln230Ter Pathogenic ★★ same condition
- CDKN1C p.Glu119Ter Pathogenic ★★ same condition
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/cdkn1c-p-ala217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown