Is CDKN1C p.Ala240fs (c.719_730delinsGTGC) pathogenic?

CDKN1C p.Ala240fs (c.719730delinsGTGC) is classified Pathogenic in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). Absent from gnomAD; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala240fs (c.719_730delinsGTGC)?

CDKN1C p.Ala240fs (c.719_730delinsGTGC) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala240fs (c.719_730delinsGTGC) in the general population?

CDKN1C p.Ala240fs (c.719_730delinsGTGC) is absent from gnomAD (gnomAD).

CDKN1C p.Ala240fs

c.719_730delinsGTGC · rs1554937726 · VCV454029

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -0.38	GERP 0.59

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala240fs
Coding: c.719_730delinsGTGC
MANE Select: NM_001122630
dbSNP: rs1554937726
Type: Indel
Location: chr11:2884727 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 240: 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.Ala240Pro Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala240Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala240Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1C p.Ala240= Likely benign ★ same residue
CDKN1C p.Ala185Leu Uncertain significance ★★ same condition
CDKN1C p.Arg222Gln Uncertain significance ★★ same condition
CDKN1C p.Glu30Leu Uncertain significance ★★ same condition
CDKN1C p.186_187AP[12] Benign/Likely benign ★★ 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-ala240fs (accessed [today's date]).

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