Is CDKN2A p.Gly89Val (c.266G>T) pathogenic?

CDKN2A p.Gly89Val (c.266G>T) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-28). AlphaMissense: likely pathogenic (0.981); No allele count reported in gnomAD v4.1 (AN 1,604,966); Associated with melanoma and neural system tumor syndrome.

What condition is associated with CDKN2A p.Gly89Val (c.266G>T)?

CDKN2A p.Gly89Val (c.266G>T) is associated with melanoma and neural system tumor syndrome (ClinVar).

How common is CDKN2A p.Gly89Val (c.266G>T) in the general population?

CDKN2A p.Gly89Val (c.266G>T) is no allele count reported in gnomAD v4.1 (AN 1,604,966) (gnomAD).

How is Melanoma and neural system tumor syndrome inherited?

Typically Autosomal dominant, Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDKN2A p.Gly89Val (c.266G>T)?

AlphaMissense predicts likely pathogenic (score 0.981) — an in-silico prediction, not a clinical call.

CDKN2A p.Gly89Val

c.266G>T · rs137854599 · VCV1802421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.981 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,966)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

melanoma and neural system tumor syndrome

Computational evidence

Protein change
AlphaMissense	0.981	likely pathogenic · top 1% in CDKN2A
REVEL	0.745	pathogenic-leaning
SaProt	LLR -19.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,604,966). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN2A
Protein: p.Gly89Val
Coding: c.266G>T
MANE Select: NM_000077
dbSNP: rs137854599
Type: single nucleotide variant
Location: chr9:21971093 (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

melanoma and neural system tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Melanoma and neural system tumor syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Adult, Elderly

Similar variants

CDKN2A p.Gly89Asp Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gly89Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly89= Conflicting classifications of pathogenicity ★ same residue
CDKN2A p.Gly89Ala Uncertain significance ★ ⚠ same residue
CDKN2A p.Gly89Cys Uncertain significance ★ ⚠ same residue
CDKN2A c.194-3653G>T Pathogenic ★★ same condition
CDKN2A c.458-105A>G Pathogenic/Likely pathogenic ★★ same condition
CDKN2A p.Arg112Gly 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-p-gly89val (accessed [today's date]).

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