Is CDKN2A p.Ala41fs (c.120del) pathogenic?

CDKN2A p.Ala41fs (c.120del) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-12). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala41fs (c.120del)?

CDKN2A p.Ala41fs (c.120del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Ala41fs (c.120del) in the general population?

CDKN2A p.Ala41fs (c.120del) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Ala41fs

c.120del · rs1554659198 · VCV487003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,886)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.52, phastCons 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,886). 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.Ala41fs
Coding: c.120del
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs1554659198
Type: Deletion
Location: chr9:21994212 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 41: 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

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

Similar variants

CDKN2A p.Pro41fs Pathogenic ★★ same residue
CDKN2A p.Ala41Thr Uncertain significance ★★ same residue
CDKN2A p.Pro41Ala Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro41Arg Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro41Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala41= Likely benign ★★ same residue
CDKN2A p.Pro41Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Pro41Leu 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-ala41fs (accessed [today's date]).

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