Is CDKN1C p.Pro273fs (c.812_815dup) pathogenic?

CDKN1C p.Pro273fs (c.812815dup) is classified Likely pathogenic in CDKN1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-04). Ultra-rare (gnomAD MAF 7.579e-07); Associated with CDKN1C-related disorder.

What condition is associated with CDKN1C p.Pro273fs (c.812_815dup)?

CDKN1C p.Pro273fs (c.812_815dup) is associated with CDKN1C-related disorder (ClinVar).

How common is CDKN1C p.Pro273fs (c.812_815dup) in the general population?

CDKN1C p.Pro273fs (c.812_815dup) is ultra-rare (gnomAD MAF 7.579e-07) (gnomAD).

CDKN1C p.Pro273fs

c.812_815dup · rs2494380120 · VCV2630051

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.579e-07)

Conditions

CDKN1C-related disorder

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 -1.1	GERP -0.53, phastCons 0.001

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

Population frequency

dbSNP / gnomAD

Global frequency 7.58e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CDKN1C
Protein: p.Pro273fs
Coding: c.812_815dup
MANE Select: NM_001122630
dbSNP: rs2494380120
Type: Duplication
Location: chr11:2884106 (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

CDKN1C-related disorder

Similar variants

CDKN1C p.Ala94fs Likely pathogenic ★ same condition
CDKN1C p.Pro273His Uncertain significance ★ ⚠ same residue
CDKN1C p.Pro273Leu Uncertain significance ★ ⚠ same residue
CDKN1C p.Arg268Ser Likely pathogenic ★★ ⚠ same condition
CDKN1C p.Ser276Leu Uncertain significance ★★ ⚠ same condition
CDKN1C p.Gln210Ter Likely pathogenic ★ same condition
CDKN1C p.Phe265Ser Likely pathogenic ★ same condition
CDKN1C p.Tyr52Ter 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-pro273fs (accessed [today's date]).

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