Is CDKN2C p.Asn159= (c.477C>T) pathogenic?

CDKN2C p.Asn159= (c.477C>T) is classified Likely benign in CDKN2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-14). Rare (popmax 0.875%, afr).

How common is CDKN2C p.Asn159= (c.477C>T) in the general population?

CDKN2C p.Asn159= (c.477C>T) is rare (popmax 0.875%, afr) (gnomAD).

CDKN2C p.Asn159=

c.477C>T · rs2500450 · VCV2638812

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.875%, afr)

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 -0.51	GERP -3.5, phastCons 0.002
Overall
CADD	8.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.875% African / African-American · 649/74,158 alleles

Filtering AF 0.819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.797%

Overall 0.0481% 761/1,581,340 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.875%	114
Middle Eastern	0.102%	977
Admixed American	0.049%	2,042
Remaining individualsnot grpmax-eligible	0.0475%	2,103
South Asian	0.00464%	21,571
European (non-Finnish)	0.00388%	25,802

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.Asn159=
Coding: c.477C>T
MANE Select: NM_078626
dbSNP: rs2500450
Type: single nucleotide variant
Location: chr1:50974240 (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.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
CDKN2C p.Asp95Glu 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-asn159 (accessed [today's date]).

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