Is CDKN1C p.Pro285= (c.855C>T) pathogenic?

CDKN1C p.Pro285= (c.855C>T) is classified Conflicting classifications of pathogenicity in CDKN1C (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00183%, nfe); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro285= (c.855C>T)?

CDKN1C p.Pro285= (c.855C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro285= (c.855C>T) in the general population?

CDKN1C p.Pro285= (c.855C>T) is very rare (popmax 0.00183%, nfe) (gnomAD).

CDKN1C p.Pro285=

c.855C>T · rs779172459 · VCV454040

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00183%, nfe)

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.093	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.051	GERP -0.2
Overall
CADD	5.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00183% European (non-Finnish) · 21/1,148,720 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000997%

Overall 0.00148% 23/1,552,096 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00183%	54,701
Remaining individualsnot grpmax-eligible	0.00167%	60,034
South Asian	0.00118%	84,534

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.Pro285=
Coding: c.855C>T
MANE Select: NM_001122630
dbSNP: rs779172459
Type: single nucleotide variant
Location: chr11:2884067 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 285: 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.Pro285Ala Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro285Arg Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro285Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1C p.Pro285His Uncertain significance ★ ⚠ same residue
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Gln219Ter Pathogenic ★★ same condition
CDKN1C p.Gln221Ter 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-pro285 (accessed [today's date]).

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