Is CDKN1C p.Pro137Arg (c.410C>G) pathogenic?

CDKN1C p.Pro137Arg (c.410C>G) is classified Uncertain significance in CDKN1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1419); Absent from gnomAD v4.1; Associated with IMAGe syndrome.

What condition is associated with CDKN1C p.Pro137Arg (c.410C>G)?

CDKN1C p.Pro137Arg (c.410C>G) is associated with IMAGe syndrome, Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro137Arg (c.410C>G) in the general population?

CDKN1C p.Pro137Arg (c.410C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Pro137Arg (c.410C>G)?

AlphaMissense predicts likely benign (score 0.1419) — an in-silico prediction, not a clinical call.

CDKN1C p.Pro137Arg

c.410C>G · rs754671425 · VCV2201987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1419 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IMAGe syndrome

Computational evidence

Protein change
AlphaMissense	0.1419	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -14.44	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.7, phastCons 1
Overall
CADD	18.77	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P148R vs ClinVar P137R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN1C
Protein: p.Pro137Arg
Coding: c.410C>G
MANE Select: NM_001122630
dbSNP: rs754671425
Type: single nucleotide variant
Location: chr11:2885047 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 137: the 'disordered' region

Full CDKN1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IMAGe syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Beckwith-Wiedemann syndrome

Similar variants

CDKN1C p.Pro137Gln Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro137Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro137= Likely benign ★ same residue
CDKN1C p.Pro137fs Pathogenic ★★ 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-pro137arg (accessed [today's date]).

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