Is CDKN2A p.Arg29= (c.87G>A) pathogenic?

CDKN2A p.Arg29= (c.87G>A) is classified Benign/Likely benign in CDKN2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0147%, afr); Associated with familial melanoma.

What condition is associated with CDKN2A p.Arg29= (c.87G>A)?

CDKN2A p.Arg29= (c.87G>A) is associated with familial melanoma, melanoma-pancreatic cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Arg29= (c.87G>A) in the general population?

CDKN2A p.Arg29= (c.87G>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Arg29=

c.87G>A · rs540871544 · VCV230671

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.47	GERP 1.1
Overall
CADD	14.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/75,034 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00632%

Overall 0.00124% 20/1,612,530 alleles · ultra-rare exomes 6/1,460,268 · genomes 14/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,821
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	8.48e-05%	1,179,786

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.Arg29=
Coding: c.87G>A
MANE Select: NM_000077
dbSNP: rs540871544
Type: single nucleotide variant
Location: chr9:21974741 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 29: an α-helix; the 'interaction with cdk5rap3 and mdm2' region

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

Disease context

familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: melanoma-pancreatic cancer syndrome hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDKN2A p.Arg29Gln Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg29Trp Uncertain significance ★★ same residue
CDKN2A p.Arg29Leu Uncertain significance ★ ⚠ same residue
CDKN2A p.Arg29Pro 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-arg29 (accessed [today's date]).

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