Is CDKN1C p.Ala248= (c.744C>T) pathogenic?

CDKN1C p.Ala248= (c.744C>T) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). Very rare (popmax 0.000177%, nfe); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala248= (c.744C>T)?

CDKN1C p.Ala248= (c.744C>T) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala248= (c.744C>T) in the general population?

CDKN1C p.Ala248= (c.744C>T) is very rare (popmax 0.000177%, nfe) (gnomAD).

CDKN1C p.Ala248=

c.744C>T · rs1590148914 · VCV760972

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000177%, nfe)

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 -0.17	GERP -1.2, phastCons 0.18
Overall
CADD	12.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000177% European (non-Finnish) · 2/1,128,930 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000148% 2/1,348,984 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.Ala248=
Coding: c.744C>T
MANE Select: NM_001122630
dbSNP: rs1590148914
Type: single nucleotide variant
Location: chr11:2884713 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 248: 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

Similar variants

CDKN1C p.Ala248Ser Uncertain significance ★★ ⚠ same residue
CDKN1C p.Ala248Thr Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala248_Asn249insAlaAlaAlaSerAla Uncertain significance ★ 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

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-ala248 (accessed [today's date]).

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