Is CDKN2A p.Val106= (c.318G>A) pathogenic?

CDKN2A p.Val106= (c.318G>A) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0415%, nfe); Associated with Maffucci syndrome.

What condition is associated with CDKN2A p.Val106= (c.318G>A)?

CDKN2A p.Val106= (c.318G>A) is associated with Maffucci syndrome, melanoma-pancreatic cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Val106= (c.318G>A) in the general population?

CDKN2A p.Val106= (c.318G>A) is ultra-rare (popmax 0.0415%, nfe) (gnomAD).

How is Maffucci syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CDKN2A p.Val106=

c.318G>A · rs199888003 · VCV135826

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0415%, nfe)

Conditions

Maffucci syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.374	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.13, phastCons 1
Overall
CADD	10.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0415% European (non-Finnish) · 490/1,179,350 alleles

Filtering AF 0.0385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0372%

Overall 0.0319% 513/1,605,694 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0415%	2,407
Remaining individualsnot grpmax-eligible	0.0241%	4,152
Admixed American	0.00668%	14,980
African / African-American	0.00534%	18,724

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.Val106=
Coding: c.318G>A
MANE Select: NM_000077
dbSNP: rs199888003
Type: single nucleotide variant
Location: chr9:21971041 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 106: the 'disordered' region; a UniProt-annotated variant site (in)

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

Disease context

Maffucci syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: melanoma-pancreatic cancer syndrome hereditary neoplastic syndrome familial melanoma

For Maffucci syndrome (Orphanet):

Inheritance: Not applicable
Onset: Childhood

Similar variants

CDKN2A p.Val106Ala Uncertain significance ★★ ⚠ same residue
CDKN2A p.Val106Glu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Val106Leu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Val106Met Uncertain significance ★★ ⚠ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A Pathogenic ★★ same condition
CDKN2A c.151-1G>C 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-val106 (accessed [today's date]).

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