Is CDKN2A p.Glu27= (c.81G>A) pathogenic?

CDKN2A p.Glu27= (c.81G>A) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-13). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Glu27= (c.81G>A)?

CDKN2A p.Glu27= (c.81G>A) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Glu27= (c.81G>A) in the general population?

CDKN2A p.Glu27= (c.81G>A) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Glu27=

c.81G>A · rs1060504184 · VCV414091

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

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 carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.66	GERP 2
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

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
Protein: p.Glu27=
Coding: c.81G>A
MANE Select: NM_000077
dbSNP: rs1060504184
Type: single nucleotide variant
Location: chr9:21974747 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 27: an α-helix; the 'interaction with cdk5rap3 and mdm2' region

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.Glu27Ter Pathogenic ★★ same residue
CDKN2A p.Glu27Ala Uncertain significance ★★ ⚠ same residue
CDKN2A p.Glu27Asp Uncertain significance ★★ ⚠ same residue
CDKN2A p.Glu27Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ile27Leu Uncertain significance ★★ same residue
CDKN2A p.Ile27Met Uncertain significance ★★ same residue
CDKN2A p.Glu27Gln Uncertain significance ★ ⚠ same residue
CDKN2A p.Glu27Lys Uncertain significance ★ ⚠ same residue

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-glu27 (accessed [today's date]).

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