Is CDKN1C p.Ala204Asp (c.611C>A) pathogenic?

CDKN1C p.Ala204Asp (c.611C>A) is classified Uncertain significance in CDKN1C (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-11). AlphaMissense: likely benign (0.1723); Very rare (popmax 0.0066%, afr); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala204Asp (c.611C>A)?

CDKN1C p.Ala204Asp (c.611C>A) is associated with Beckwith-Wiedemann syndrome, IMAGe syndrome (ClinVar).

How common is CDKN1C p.Ala204Asp (c.611C>A) in the general population?

CDKN1C p.Ala204Asp (c.611C>A) is very rare (popmax 0.0066%, afr) (gnomAD).

What do computational predictors say about CDKN1C p.Ala204Asp (c.611C>A)?

AlphaMissense predicts likely benign (score 0.1723) — an in-silico prediction, not a clinical call.

CDKN1C p.Ala204Asp

c.611C>A · rs1060500176 · VCV404245

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0066%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.1723	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -11.38	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 -0.003	GERP -1.2
Overall
CADD	12.24	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 A215D vs ClinVar A204D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0066% African / African-American · 4/60,638 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.000434% 5/1,151,808 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0066%	15,160
European (non-Finnish)	0.000107%	934,352

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.Ala204Asp
Coding: c.611C>A
MANE Select: NM_001122630
dbSNP: rs1060500176
Type: single nucleotide variant
Location: chr11:2884846 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 204: the '9 x 4 aa repeats of p-a-p-a' region; 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

Also linked: IMAGe syndrome

Similar variants

CDKN1C p.Ala204Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala204Val Uncertain significance ★ ⚠ 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
CDKN1C p.Gln221Ter Pathogenic ★★ same condition
CDKN1C p.Gln230Ter 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-ala204asp (accessed [today's date]).

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