Is CDKN1C p.Ala112= (c.336T>A) pathogenic?

CDKN1C p.Ala112= (c.336T>A) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Absent from gnomAD v4.1; Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala112= (c.336T>A)?

CDKN1C p.Ala112= (c.336T>A) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala112= (c.336T>A) in the general population?

CDKN1C p.Ala112= (c.336T>A) is absent from gnomAD v4.1 (gnomAD).

CDKN1C p.Ala112=

c.336T>A · rs2494388669 · VCV2051324

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -0.16
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

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.Ala112=
Coding: c.336T>A
MANE Select: NM_001122630
dbSNP: rs2494388669
Type: single nucleotide variant
Location: chr11:2885121 (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.Ala112Ser Uncertain significance ★★ ⚠ same residue
CDKN1C p.Ala112Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala112Val Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala112fs Likely pathogenic ★ 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

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-ala112 (accessed [today's date]).

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