Is CDKN1C p.Pro175fs (c.522_526del) pathogenic?

CDKN1C p.Pro175fs (c.522526del) is classified Likely benign in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-26). Ultra-rare (popmax 0.0101%, sas); Associated with Beckwith-Wiedemann syndrome.

What condition is associated with CDKN1C p.Pro175fs (c.522_526del)?

CDKN1C p.Pro175fs (c.522_526del) is associated with Beckwith-Wiedemann syndrome (ClinVar).

How common is CDKN1C p.Pro175fs (c.522_526del) in the general population?

CDKN1C p.Pro175fs (c.522_526del) is ultra-rare (popmax 0.0101%, sas) (gnomAD).

CDKN1C p.Pro175fs

c.522_526del · rs1590149916 · VCV733277

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, sas)

Conditions

Beckwith-Wiedemann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.3	GERP -0.76, phastCons 0.002
Region caveats
Repeat context	tandem	G-rich low complexity, simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% South Asian · 2/19,822 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000723%

Overall 0.00153% 12/786,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0101%	9,911
European (non-Finnish)	0.00132%	75,528

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.Pro175fs
Coding: c.522_526del
MANE Select: NM_001122630
dbSNP: rs1590149916
Type: Deletion
Location: chr11:2884931 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.93
Residue 175: 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

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

Similar variants

CDKN1C p.Pro175Ala Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro175Leu Uncertain significance ★ same residue
CDKN1C p.Pro175= Likely benign ★ same residue
CDKN1C p.Pro137fs Pathogenic ★★ same condition
CDKN1C p.Ser73fs Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Val130fs Pathogenic/Likely pathogenic ★★ same condition
CDKN1C p.Ala246_Ala252del Uncertain significance ★★ same condition
CDKN1C p.Gly242_Ala245del Uncertain significance ★★ 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-pro175fs (accessed [today's date]).

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