CDKN1C p.Leu304=
c.912G>T · rs2133779878 · VCV1104493
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00191%, amr)
Conditions
1
Beckwith-Wiedemann syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.49 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 0.93, phastCons 1 |
| Overall | ||
| CADD | 14.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00191%
Admixed American · 1/52,406 alleles
Overall
7.11e-05%
1/1,405,996 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.Leu304=
- Coding
- c.912G>T
- MANE Select
- NM_001122630
- dbSNP
- rs2133779878
- Type
- single nucleotide variant
- Location
- chr11:2884010 (GRCh38)
- Gene constraint
- LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.93
- Residue 304
- the 'disordered' region
Similar variants
- 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
- CDKN1C p.Pro59Leu Pathogenic/Likely 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-leu304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown