Is CDKN2A p.Gly89= (c.267C>T) pathogenic?

CDKN2A p.Gly89= (c.267C>T) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-26). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gly89= (c.267C>T)?

CDKN2A p.Gly89= (c.267C>T) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Gly89= (c.267C>T) in the general population?

CDKN2A p.Gly89= (c.267C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CDKN2A p.Gly89=

c.267C>T · rs1404957845 · VCV532269

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.33	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.048	GERP -3, phastCons 0.26
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,000 alleles

Overall 0.000125% 2/1,604,884 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,000
European (non-Finnish)	8.48e-05%	1,179,578

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.Gly89=
Coding: c.267C>T
MANE Select: NM_000077
dbSNP: rs1404957845
Type: single nucleotide variant
Location: chr9:21971092 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 89: a UniProt-annotated variant site (in cmm2; somatic mutation); a UniProt-annotated variant site (in cmm2); the 'disordered' 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: familial melanoma

Similar variants

CDKN2A p.Gly89Asp Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gly89Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly89Ala Uncertain significance ★ ⚠ same residue
CDKN2A p.Gly89Cys Uncertain significance ★ ⚠ same residue
CDKN2A p.Gly89Val 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-gly89 (accessed [today's date]).

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