Is CDKN2A p.Val7= (c.21G>C) pathogenic?

CDKN2A p.Val7= (c.21G>C) is classified Benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). Absent from gnomAD v4.1; Associated with melanoma-pancreatic cancer syndrome.

What condition is associated with CDKN2A p.Val7= (c.21G>C)?

CDKN2A p.Val7= (c.21G>C) is associated with melanoma-pancreatic cancer syndrome (ClinVar).

How common is CDKN2A p.Val7= (c.21G>C) in the general population?

CDKN2A p.Val7= (c.21G>C) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Val7=

Q: How is Familial atypical multiple mole melanoma syndrome inherited?

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

c.21G>C · VCV4294143

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

melanoma-pancreatic cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -1.6, phastCons 0.99
Overall
CADD	8.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN2A
Protein: p.Val7=
Coding: c.21G>C
MANE Select: NM_000077 · reported on NM_058195
Type: single nucleotide variant
Location: chr9:21994311 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 7: a modified residue (phosphoserine); the 'interaction with cdk5rap3 and mdm2' region

Full CDKN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

melanoma-pancreatic cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial atypical multiple mole melanoma syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

CDKN2A p.Ser7= Benign ★ same residue
CDKN2A p.Ser7fs Pathogenic ★ same residue
CDKN2A p.Ser7Arg Uncertain significance ★ ⚠ same residue
CDKN2A p.Ser7Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Val7Ala Uncertain significance ★ same residue
CDKN2A p.Ser7Asn Likely benign ★ ⚠ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G 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-val7 (accessed [today's date]).

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