CDKN1C p.Pro181=
c.543G>A · rs2133783693 · VCV1476632
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000692%, nfe)
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 -3.1 | GERP -0.78 |
| Overall | ||
| CADD | 7.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000692%
European (non-Finnish) · 5/722,962 alleles
Filtering AF
0.000203%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000147%
Overall
0.000679%
5/736,770 alleles · very rare
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.Pro181=
- Coding
- c.543G>A
- MANE Select
- NM_001122630
- dbSNP
- rs2133783693
- Type
- single nucleotide variant
- Location
- chr11:2884914 (GRCh38)
- Gene constraint
- LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.93
- Residue 181
- 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.Pro181Arg Uncertain significance ★★ ⚠ same residue
- CDKN1C p.Pro181Ser Uncertain significance ★ ⚠ same residue
- CDKN1C p.Pro181fs Pathogenic ★ same residue
- CDKN1C p.Pro181_Ala182insSerPro Likely benign ★ 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
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-pro181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown