Is CDKN1C p.Pro141Arg (c.422C>G) pathogenic?

CDKN1C p.Pro141Arg (c.422C>G) is classified Uncertain significance in CDKN1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1854); Very rare (popmax 0.00315%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDKN1C p.Pro141Arg (c.422C>G)?

CDKN1C p.Pro141Arg (c.422C>G) is associated with Inborn genetic diseases, Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro141Arg (c.422C>G) in the general population?

CDKN1C p.Pro141Arg (c.422C>G) is very rare (popmax 0.00315%, eas) (gnomAD).

What do computational predictors say about CDKN1C p.Pro141Arg (c.422C>G)?

AlphaMissense predicts likely benign (score 0.1854) — an in-silico prediction, not a clinical call.

CDKN1C p.Pro141Arg

c.422C>G · rs1848953520 · VCV1482381

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00315%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1854	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -11.21	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 1.2	GERP 0.41, phastCons 0.91
Overall
CADD	18.6	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 P152R vs ClinVar P141R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00315% East Asian · 1/31,772 alleles

Overall 8.61e-05% 1/1,161,944 alleles · very rare

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.Pro141Arg
Coding: c.422C>G
MANE Select: NM_001122630
dbSNP: rs1848953520
Type: single nucleotide variant
Location: chr11:2885035 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 141: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Beckwith-Wiedemann syndrome

Similar variants

CDKN1C p.Pro141Ala Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro141Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro141Ser Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro141Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro141= Likely benign ★ same residue
CDKN1C p.Pro141fs Pathogenic ★ same residue
CDKN1C p.Pro141_Val184del Likely benign ★ same residue
CDKN1C p.Asp263Asn 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-pro141arg (accessed [today's date]).

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