Is CDKN2A p.Ala143Val (c.428C>T) pathogenic?

CDKN2A p.Ala143Val (c.428C>T) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-10). AlphaMissense: likely benign (0.1113); Absent from gnomAD v4.1; Associated with melanoma and neural system tumor syndrome.

What condition is associated with CDKN2A p.Ala143Val (c.428C>T)?

CDKN2A p.Ala143Val (c.428C>T) is associated with melanoma and neural system tumor syndrome, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Ala143Val (c.428C>T) in the general population?

CDKN2A p.Ala143Val (c.428C>T) is absent from gnomAD v4.1 (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.Ala143Val (c.428C>T)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

CDKN2A p.Ala143Val

c.428C>T · rs767149947 · VCV1739412

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,392)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

melanoma and neural system tumor syndrome

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -0.56
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	11.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 1,612,392). 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.Ala143Val
Coding: c.428C>T
MANE Select: NM_000077
dbSNP: rs767149947
Type: single nucleotide variant
Location: chr9:21970931 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 143: a turn

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

Also linked: hereditary neoplastic syndrome

For Melanoma and neural system tumor syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Adult, Elderly

Similar variants

CDKN2A p.Ala143Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala143= Likely benign ★★ same residue
CDKN2A p.Ala143Ser Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala143Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A c.150+2T>G Likely 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

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-ala143val (accessed [today's date]).

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