Is CDKN1C p.Pro169= (c.507G>A) pathogenic?

CDKN1C p.Pro169= (c.507G>A) is classified Likely benign in CDKN1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-07). Ultra-rare (popmax 0.017%, eas); Associated with IMAGe syndrome.

What condition is associated with CDKN1C p.Pro169= (c.507G>A)?

CDKN1C p.Pro169= (c.507G>A) is associated with IMAGe syndrome, Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro169= (c.507G>A) in the general population?

CDKN1C p.Pro169= (c.507G>A) is ultra-rare (popmax 0.017%, eas) (gnomAD).

CDKN1C p.Pro169=

c.507G>A · rs1419249357 · VCV524710

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, eas)

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 -0.7	GERP -0.91
Overall
CADD	8.408	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% East Asian · 4/23,500 alleles

Filtering AF 0.00576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00519% 53/1,020,274 alleles · ultra-rare exomes 49/874,284 · genomes 4/145,990 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.017%	5,875
Remaining individualsnot grpmax-eligible	0.0139%	7,191
European (non-Finnish)	0.00513%	19,478
Admixed American	0.00484%	20,656
African / African-American	0.00174%	57,608

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.Pro169=
Coding: c.507G>A
MANE Select: NM_001122630
dbSNP: rs1419249357
Type: single nucleotide variant
Location: chr11:2884950 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 169: the '9 x 4 aa repeats of p-a-p-a' region

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.Pro169Arg Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro169Gln Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro169Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro169Ser 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

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-pro169 (accessed [today's date]).

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