Is CDKN2A p.Ser43Ter (c.126dup) pathogenic?

CDKN2A p.Ser43Ter (c.126dup) is classified Pathogenic in CDKN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-19). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ser43Ter (c.126dup)?

CDKN2A p.Ser43Ter (c.126dup) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Ser43Ter (c.126dup) in the general population?

CDKN2A p.Ser43Ter (c.126dup) is absent from gnomAD (gnomAD).

CDKN2A p.Ser43Ter

c.126dup · rs2131112280 · VCV1069074

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.62	GERP -3.3, phastCons 0.65

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser43Ter
Coding: c.126dup
MANE Select: NM_000077
dbSNP: rs2131112280
Type: Duplication
Location: chr9:21974701 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 43: a β-strand; 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: melanoma-pancreatic cancer syndrome familial melanoma

Similar variants

CDKN2A p.Ser43_Tyr44insTer Pathogenic ★★ same residue
CDKN2A p.Ser43Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ser43Thr Uncertain significance ★★ ⚠ same residue
CDKN2A p.Val43Leu Uncertain significance ★★ same residue
CDKN2A p.Ser43= Benign/Likely benign ★★ same residue
CDKN2A p.Val43fs Pathogenic ★ same residue
CDKN2A p.Ser43Asn Uncertain significance ★ ⚠ same residue
CDKN2A p.Val43Ala 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-ser43ter (accessed [today's date]).

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