Is CDKN1C p.Ala18Val (c.53C>T) pathogenic?

CDKN1C p.Ala18Val (c.53C>T) is classified Uncertain significance in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-28). AlphaMissense: ambiguous (0.3808); Absent from gnomAD v4.1; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala18Val (c.53C>T)?

CDKN1C p.Ala18Val (c.53C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala18Val (c.53C>T) in the general population?

CDKN1C p.Ala18Val (c.53C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN1C p.Ala18Val (c.53C>T)?

AlphaMissense predicts ambiguous (score 0.3808) — an in-silico prediction, not a clinical call.

CDKN1C p.Ala18Val

c.53C>T · rs1319614382 · VCV1357116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3808 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
AlphaMissense	0.3808	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.056, phastCons 1
Overall
CADD	18.86	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 A29V vs ClinVar A18V) — 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.Ala18Val
Coding: c.53C>T
MANE Select: NM_001122630
dbSNP: rs1319614382
Type: single nucleotide variant
Location: chr11:2885404 (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

Similar variants

CDKN1C p.Ala18= Likely benign ★ same residue
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
CDKN1C p.Glu119Ter Pathogenic ★★ same condition
CDKN1C p.Glu214Ter 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-ala18val (accessed [today's date]).

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