Is CDKN2A p.Asp156= (c.468T>C) pathogenic?

CDKN2A p.Asp156= (c.468T>C) is classified Benign/Likely benign in CDKN2A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-10). Very rare (popmax 0.0022%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Asp156= (c.468T>C)?

CDKN2A p.Asp156= (c.468T>C) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Asp156= (c.468T>C) in the general population?

CDKN2A p.Asp156= (c.468T>C) is very rare (popmax 0.0022%, sas) (gnomAD).

CDKN2A p.Asp156=

c.468T>C · rs749753811 · VCV215633

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

hereditary neoplastic 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 -0.9	GERP -2
Overall
CADD	1.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000248% 4/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.000169%	589,981

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: CDKN2A
Protein: p.Asp156=
Coding: c.468T>C
MANE Select: NM_000077
dbSNP: rs749753811
Type: single nucleotide variant
Location: chr9:21968232 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB

Full CDKN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: melanoma-pancreatic cancer syndrome familial melanoma

Similar variants

CDKN2A p.Asp156Tyr Uncertain significance ★★ ⚠ same residue
CDKN2A p.Asp156Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Asp156Glu Uncertain significance ★ ⚠ same residue
CDKN2A p.Asp156Val Uncertain significance ★ ⚠ same residue
CDKN2A p.Asp156fs Uncertain significance ★ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A 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/cdkn2a-p-asp156 (accessed [today's date]).

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