Is CDKN1C p.Pro139fs (c.416del) pathogenic?

CDKN1C p.Pro139fs (c.416del) is classified Pathogenic/Likely pathogenic in CDKN1C (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-11-05). Absent from gnomAD v4.1; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro139fs (c.416del)?

CDKN1C p.Pro139fs (c.416del) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro139fs (c.416del) in the general population?

CDKN1C p.Pro139fs (c.416del) is absent from gnomAD v4.1 (gnomAD).

CDKN1C p.Pro139fs

c.416del · rs786205234 · VCV192352

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,317,402)

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.31	GERP -0.94, phastCons 0.023
Region caveats
Repeat context	tandem	G-rich low complexity, simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,317,402). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN1C
Protein: p.Pro139fs
Coding: c.416del
MANE Select: NM_001122630
dbSNP: rs786205234
Type: Deletion
Location: chr11:2885041 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 139: the 'disordered' region

Full CDKN1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Beckwith-Wiedemann syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDKN1C p.Pro139Gln Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro139Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro139= Likely benign ★ same residue
CDKN1C p.Pro137fs Pathogenic ★★ same condition
CDKN1C p.Ser73fs Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Val130fs Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Ala246_Ala252del Uncertain significance ★★ same condition
CDKN1C p.Gly242_Ala245del Uncertain significance ★★ 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-pro139fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown