Is CDKN1C p.Ala148= (c.444C>A) pathogenic?

CDKN1C p.Ala148= (c.444C>A) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Ultra-rare (popmax 0.0318%, mid); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Ala148= (c.444C>A)?

CDKN1C p.Ala148= (c.444C>A) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Ala148= (c.444C>A) in the general population?

CDKN1C p.Ala148= (c.444C>A) is ultra-rare (popmax 0.0318%, mid) (gnomAD).

CDKN1C p.Ala148=

c.444C>A · rs1590150329 · VCV700297

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, mid)

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 0.21	GERP 0.31
Overall
CADD	6.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0318% Middle Eastern · 1/3,140 alleles

Filtering AF 9.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.6e-05%

Overall 0.000479% 5/1,042,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0318%	3,140
European (non-Finnish)	0.00042%	237,921

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.Ala148=
Coding: c.444C>A
MANE Select: NM_001122630
dbSNP: rs1590150329
Type: single nucleotide variant
Location: chr11:2885013 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 148: 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.Ala148Pro Uncertain significance ★★ ⚠ same residue
CDKN1C p.Ala148Thr Uncertain significance ★★ ⚠ same residue
CDKN1C p.Ala148Asp Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala148Gly Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala148Val Uncertain significance ★ ⚠ same residue
CDKN1C p.Ala148_Pro157del Likely benign ★ 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-ala148 (accessed [today's date]).

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