CDKN1C p.Ala188=
c.564C>T · rs1554937891 · VCV524743
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00591%, amr)
Conditions
2
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 -1.2 | GERP -0.69 |
| Overall | ||
| CADD | 6.816 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00591%
Admixed American · 1/16,916 alleles
Overall
0.000342%
3/877,744 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00591% | 16,916 |
| South Asian | 0.0051% | 19,616 |
| European (non-Finnish) | 0.000138% | 725,658 |
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.Ala188=
- Coding
- c.564C>T
- MANE Select
- NM_001122630
- dbSNP
- rs1554937891
- Type
- single nucleotide variant
- Location
- chr11:2884893 (GRCh38)
- Gene constraint
- LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.93
- Residue 188
- the '9 x 4 aa repeats of p-a-p-a' region; the 'disordered' region
Similar variants
- CDKN1C p.Ala188Thr Uncertain significance ★ ⚠ same residue
- CDKN1C p.Ala188_Pro193delinsValAlaValAlaValLeu Likely benign ★ same residue
- CDKN1C p.Arg268Ser Likely pathogenic ★★ ⚠ same condition
- 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
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-ala188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown