Is CDKN2A p.Ala60Val (c.179C>T) pathogenic?

CDKN2A p.Ala60Val (c.179C>T) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). AlphaMissense: ambiguous (0.4418); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala60Val (c.179C>T)?

CDKN2A p.Ala60Val (c.179C>T) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Ala60Val (c.179C>T) in the general population?

CDKN2A p.Ala60Val (c.179C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Ala60Val (c.179C>T)?

AlphaMissense predicts ambiguous (score 0.4418) — an in-silico prediction, not a clinical call.

CDKN2A p.Ala60Val

c.179C>T · rs36204594 · VCV570547

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4418 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,852)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4418	ambiguous
REVEL	0.583	indeterminate
SaProt	LLR -6.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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 1,596,852). 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.Ala60Val
Coding: c.179C>T
MANE Select: NM_000077
dbSNP: rs36204594
Type: single nucleotide variant
Location: chr9:21971180 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 60: an α-helix; a UniProt-annotated variant site (in); a UniProt-annotated variant site (in melanoma; loss of cdk4 binding); the 'interaction with cdk5rap3 and mdm2' region; 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: melanoma-pancreatic cancer syndrome familial melanoma

Similar variants

CDKN2A p.Ala60= Uncertain significance ★★ same residue
CDKN2A p.Ala60Thr Uncertain significance ★★ ⚠ same residue
CDKN2A p.Leu60Ile Uncertain significance ★★ same residue
CDKN2A p.Leu60Phe Uncertain significance ★★ same residue
CDKN2A p.Ala60Glu Likely pathogenic ★ same residue
CDKN2A p.Ala60Pro Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala60Ser Uncertain significance ★ same residue
CDKN2A p.Leu60Arg 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-ala60val (accessed [today's date]).

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