CDKN1C p.Ala182=
c.546T>C · rs1412788622 · VCV524724
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00989%, eas)
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 -0.63 | GERP -0.79, phastCons 0.002 |
| Overall | ||
| CADD | 5.651 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00989%
East Asian · 1/10,116 alleles
Filtering AF
0.000515%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000372%
Overall
0.00149%
12/803,674 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00989% | 10,116 |
| Remaining individualsnot grpmax-eligible | 0.00771% | 12,969 |
| South Asian | 0.0058% | 17,242 |
| European (non-Finnish) | 0.0012% | 83,442 |
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.Ala182=
- Coding
- c.546T>C
- MANE Select
- NM_001122630
- dbSNP
- rs1412788622
- Type
- single nucleotide variant
- Location
- chr11:2884911 (GRCh38)
- Gene constraint
- LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.93
- Residue 182
- the '9 x 4 aa repeats of p-a-p-a' region; the 'disordered' region; a UniProt-annotated variant site (in hepatocellular carcinomas)
Similar variants
- CDKN1C p.Ala182Ser 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
- CDKN1C p.Glu214Ter 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-ala182 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown