Is CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1]) pathogenic?

CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1]) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Ultra-rare (popmax 0.0145%, sas); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1])?

CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1]) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1]) in the general population?

CDKN1C p.152APVA[1] (c.455CTCCGGTCGCGG[1]) is ultra-rare (popmax 0.0145%, sas) (gnomAD).

CDKN1C p.152APVA[1]

c.455CTCCGGTCGCGG[1] · rs565544512 · VCV454006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, sas)

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.093	GERP -0.57
Overall
CADD	9.31	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	G-rich low complexity, simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0145% South Asian · 3/20,720 alleles

Filtering AF 0.00393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00224% 22/981,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0145%	6,907
Remaining individualsnot grpmax-eligible	0.0083%	12,053
East Asian	0.00775%	12,910
Admixed American	0.00477%	20,952
African / African-American	0.00187%	53,392
European (non-Finnish)	0.00154%	64,934

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.152APVA[1]
Coding: c.455CTCCGGTCGCGG[1]
MANE Select: NM_001122630
dbSNP: rs565544512
Type: Microsatellite
Location: chr11:2884967 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93

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.128VP[1] Uncertain significance ★★ same condition
CDKN1C p.152APVA[2] Benign/Likely benign ★★ same condition
CDKN1C p.Ala159fs Likely pathogenic ★ same condition
CDKN1C p.Arg270fs Pathogenic ★ same condition
CDKN1C p.Ser212fs Pathogenic ★ same condition
CDKN1C p.128VP[3] Uncertain significance ★ same condition
CDKN1C p.131PA[1] Uncertain significance ★ same condition
CDKN1C p.131PA[3] 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-152apva-1 (accessed [today's date]).

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