Is CDKN1C p.Pro203Gln (c.608C>A) pathogenic?

CDKN1C p.Pro203Gln (c.608C>A) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.1478); Very rare (popmax 0.0081%, eas); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro203Gln (c.608C>A)?

CDKN1C p.Pro203Gln (c.608C>A) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro203Gln (c.608C>A) in the general population?

CDKN1C p.Pro203Gln (c.608C>A) is very rare (popmax 0.0081%, eas) (gnomAD).

What do computational predictors say about CDKN1C p.Pro203Gln (c.608C>A)?

AlphaMissense predicts likely benign (score 0.1478) — an in-silico prediction, not a clinical call.

CDKN1C p.Pro203Gln

c.608C>A · rs1564929606 · VCV1489189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1478 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0081%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.1478	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -12.08	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 -0.14	GERP 0.58
Overall
CADD	15.41	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 P214Q vs ClinVar P203Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0081% East Asian · 2/24,682 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000601%

Overall 0.0002% 2/1,001,466 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.Pro203Gln
Coding: c.608C>A
MANE Select: NM_001122630
dbSNP: rs1564929606
Type: single nucleotide variant
Location: chr11:2884849 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 203: the '9 x 4 aa repeats of p-a-p-a' region; the 'disordered' region; a UniProt-annotated variant site (in a bladder cancer)

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.Pro203Ala Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro203Ser Uncertain significance ★★ ⚠ same residue
CDKN1C p.Pro203Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro203Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro203= Likely benign ★ same residue
CDKN1C p.Pro203fs Pathogenic same residue
CDKN1C p.Asp263Asn Pathogenic ★★ ⚠ same condition
CDKN1C p.Cys19Ter Pathogenic/Likely 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-pro203gln (accessed [today's date]).

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