Is CDKN2C p.Pro63= (c.189C>T) pathogenic?

CDKN2C p.Pro63= (c.189C>T) is classified Likely benign in CDKN2C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Ultra-rare (popmax 0.025%, amr).

How common is CDKN2C p.Pro63= (c.189C>T) in the general population?

CDKN2C p.Pro63= (c.189C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

CDKN2C p.Pro63=

c.189C>T · rs752677434 · VCV3026540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

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 0.16	GERP -2.6, phastCons 0.95
Overall
CADD	11.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/60,000 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00223% 36/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,000
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)	0.0011%	90,771

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: CDKN2C
Protein: p.Pro63=
Coding: c.189C>T
MANE Select: NM_078626
dbSNP: rs752677434
Type: single nucleotide variant
Location: chr1:50973952 (GRCh38)
Gene constraint: LOEUF 0.94 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 6 PDB

Full CDKN2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2C p.Asn159= Likely benign ★★ same type
CDKN2C p.Ala127Asp Uncertain significance ★ ⚠ same type
CDKN2C p.Ala161Gly Uncertain significance ★ ⚠ same type
CDKN2C p.Ala77Val Uncertain significance ★ ⚠ same type
CDKN2C p.Arg39Ser Uncertain significance ★ ⚠ same type
CDKN2C p.Asp17His Uncertain significance ★ ⚠ same type
CDKN2C p.Asp17Tyr Uncertain significance ★ ⚠ same type
CDKN2C p.Asp64His Uncertain significance ★ ⚠ same type

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/cdkn2c-p-pro63 (accessed [today's date]).

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