Is CDKN1C p.Pro193fs (c.578del) pathogenic?

CDKN1C p.Pro193fs (c.578del) is classified Pathogenic in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-05). Absent from gnomAD v4.1; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro193fs (c.578del)?

CDKN1C p.Pro193fs (c.578del) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro193fs (c.578del) in the general population?

CDKN1C p.Pro193fs (c.578del) is absent from gnomAD v4.1 (gnomAD).

CDKN1C p.Pro193fs

c.578del · rs2133783249 · VCV1402309

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 885,706)

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 -1.7	GERP -0.71
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 885,706). 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.Pro193fs
Coding: c.578del
MANE Select: NM_001122630
dbSNP: rs2133783249
Type: Deletion
Location: chr11:2884879 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 193: the '9 x 4 aa repeats of p-a-p-a' region; 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.Pro193Leu Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro193_Ala194insValAla Uncertain significance ★ same residue
CDKN1C p.Pro193Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1C p.Pro193Arg Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro193Gln Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro193= Likely benign ★ same residue
CDKN1C p.Pro137fs Pathogenic ★★ same condition
CDKN1C p.Ser73fs 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-pro193fs (accessed [today's date]).

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