Is CDKN1C p.Glu70fs (c.206_207insA) pathogenic?

CDKN1C p.Glu70fs (c.206207insA) is classified Pathogenic in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Glu70fs (c.206_207insA)?

CDKN1C p.Glu70fs (c.206_207insA) is associated with Beckwith-Wiedemann syndrome (ClinVar).

CDKN1C p.Glu70fs

c.206_207insA · VCV3660058

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 0.42	GERP -1.9, phastCons 0.99

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

Variant & gene context

Gene: CDKN1C
Protein: p.Glu70fs
Coding: c.206_207insA
MANE Select: NM_001122630
Type: Insertion
Location: chr11:2885250 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 70: a UniProt-annotated variant site (in bws)

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.Glu70Gln Uncertain significance ★ ⚠ same residue
CDKN1C p.Glu70Lys Uncertain significance ★ ⚠ same residue
CDKN1C c.*5+19_*5+20insA Likely benign ★★ same condition
CDKN1C p.Asn43fs Pathogenic ★ same condition
CDKN1C p.Asp53fs Pathogenic ★ same condition
CDKN1C p.Phe23Ter Pathogenic ★ same condition
CDKN1C p.Phe264fs Pathogenic ★ same condition
CDKN1C p.Pro141fs 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-glu70fs (accessed [today's date]).

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