Is CDKN2A p.Val24Ala (c.71T>C) pathogenic?

CDKN2A p.Val24Ala (c.71T>C) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-23). Very rare (popmax 0.0077%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Val24Ala (c.71T>C)?

CDKN2A p.Val24Ala (c.71T>C) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Val24Ala (c.71T>C) in the general population?

CDKN2A p.Val24Ala (c.71T>C) is very rare (popmax 0.0077%, sas) (gnomAD).

CDKN2A p.Val24Ala

c.71T>C · rs749723804 · VCV1407597

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.467	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.37, phastCons 1
Overall
CADD	19.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0077% South Asian · 7/90,914 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000482% 7/1,453,488 alleles · very rare

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.Val24Ala
Coding: c.71T>C
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs749723804
Type: single nucleotide variant
Location: chr9:21994261 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 24: a UniProt-annotated variant site (in cmm2); a UniProt-annotated variant site (found in a patient with multiple primary melanoma; partial loss of cdk4 binding); 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: familial melanoma

Similar variants

CDKN2A p.Arg24Pro Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Arg24Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg24Leu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg24= Benign/Likely benign ★★ same residue
CDKN2A p.Val24= Benign/Likely benign ★★ same residue
CDKN2A p.Arg24Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Arg24Trp Uncertain significance ★ ⚠ same residue
CDKN2A p.Val24Leu 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-val24ala (accessed [today's date]).

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