Is CDKN1C p.Arg33= (c.99C>T) pathogenic?

CDKN1C p.Arg33= (c.99C>T) is classified Benign/Likely benign in CDKN1C (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.711%, afr); Associated with IMAGe syndrome.

What condition is associated with CDKN1C p.Arg33= (c.99C>T)?

CDKN1C p.Arg33= (c.99C>T) is associated with IMAGe syndrome, Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Arg33= (c.99C>T) in the general population?

CDKN1C p.Arg33= (c.99C>T) is rare (popmax 0.711%, afr) (gnomAD).

CDKN1C p.Arg33=

c.99C>T · rs149717696 · VCV236949

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.711%, afr)

Conditions

IMAGe 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 -0.14	GERP -2.3, phastCons 0.2
Overall
CADD	8.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.711% African / African-American · 530/74,548 alleles

Filtering AF 0.661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.641%

Overall 0.0393% 624/1,589,398 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.711%	141
Admixed American	0.073%	1,369
Remaining individualsnot grpmax-eligible	0.0666%	1,502
Middle Eastern	0.0166%	6,036
South Asian	0.00455%	21,965
European (non-Finnish)	0.000513%	195,087

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.Arg33=
Coding: c.99C>T
MANE Select: NM_001122630
dbSNP: rs149717696
Type: single nucleotide variant
Location: chr11:2885358 (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

IMAGe syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Beckwith-Wiedemann syndrome

Similar variants

CDKN1C p.Arg33Cys Uncertain significance ★★ ⚠ same residue
CDKN1C p.Arg33Leu Uncertain significance ★★ ⚠ same residue
CDKN1C p.Arg33His 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

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-arg33 (accessed [today's date]).

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