Is CDKN1C p.Pro106Arg (c.317C>G) pathogenic?

CDKN1C p.Pro106Arg (c.317C>G) is classified Uncertain significance in CDKN1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1849); Very rare (popmax 0.00909%, nfe); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro106Arg (c.317C>G)?

CDKN1C p.Pro106Arg (c.317C>G) is associated with Beckwith-Wiedemann syndrome, IMAGe syndrome (ClinVar).

How common is CDKN1C p.Pro106Arg (c.317C>G) in the general population?

CDKN1C p.Pro106Arg (c.317C>G) is very rare (popmax 0.00909%, nfe) (gnomAD).

What do computational predictors say about CDKN1C p.Pro106Arg (c.317C>G)?

AlphaMissense predicts likely benign (score 0.1849) — an in-silico prediction, not a clinical call.

CDKN1C p.Pro106Arg

c.317C>G · rs945890937 · VCV453995

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00909%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.1849	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.95, phastCons 1
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P117R vs ClinVar P106R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00909% European (non-Finnish) · 103/1,133,142 alleles

Filtering AF 0.00763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00712%

Overall 0.0072% 108/1,499,954 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00909%	11,001
Remaining individualsnot grpmax-eligible	0.00515%	19,424
African / African-American	0.00143%	69,714
South Asian	0.00128%	78,224

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.Pro106Arg
Coding: c.317C>G
MANE Select: NM_001122630
dbSNP: rs945890937
Type: single nucleotide variant
Location: chr11:2885140 (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

Also linked: IMAGe syndrome

Similar variants

CDKN1C p.Pro106Leu Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro106Ser Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro106Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN1C p.Pro106= Likely benign ★ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ same condition
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C p.Cys19Ter Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Gln219Ter 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-pro106arg (accessed [today's date]).

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