Is CDKN2A c.150+2T>G pathogenic?

CDKN2A c.150+2T>G is classified Likely pathogenic in CDKN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-14). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A c.150+2T>G?

CDKN2A c.150+2T>G is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome (ClinVar).

How common is CDKN2A c.150+2T>G in the general population?

CDKN2A c.150+2T>G is absent from gnomAD v4.1 (gnomAD).

CDKN2A c.150+2T>G

rs1060501265 · VCV1773995

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.80	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.9	GERP 0.85, phastCons 1
Non-coding constraint	Z 5.22	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN2A
Coding: c.150+2T>G
MANE Select: NM_000077
dbSNP: rs1060501265
Type: single nucleotide variant
Location: chr9:21974676 (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

Similar variants

CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A Pathogenic ★★ same condition
CDKN2A c.151-1G>C Pathogenic ★★ same condition
CDKN2A c.151-1G>T Pathogenic/Likely pathogenic ★★ same condition
CDKN2A c.151-2A>G Pathogenic/Likely pathogenic ★★ same condition
CDKN2A c.193+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDKN2A c.193+2T>C Likely pathogenic ★★ same condition
CDKN2A c.193+5G>A Pathogenic/Likely 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-c-150-plus-2t-g (accessed [today's date]).

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