Is CDKN2A p.Arg21Glu (c.61_62delinsGA) pathogenic?

CDKN2A p.Arg21Glu (c.6162delinsGA) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-14). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Arg21Glu (c.61_62delinsGA)?

CDKN2A p.Arg21Glu (c.61_62delinsGA) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Arg21Glu (c.61_62delinsGA) in the general population?

CDKN2A p.Arg21Glu (c.61_62delinsGA) is absent from gnomAD (gnomAD).

CDKN2A p.Arg21Glu

c.61_62delinsGA · rs2489327871 · VCV1751628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 1.5, phastCons 0.8

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.Arg21Glu
Coding: c.61_62delinsGA
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2489327871
Type: Indel
Location: chr9:21994270 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 21: 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.Ala21Asp Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala21Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala21Thr Uncertain significance ★★ same residue
CDKN2A p.Ala21Val Uncertain significance ★★ same residue
CDKN2A p.Arg21Lys Uncertain significance ★★ same residue
CDKN2A p.Ala21_Arg22insAlaAla Uncertain significance ★ same residue
CDKN2A p.Arg21Trp Uncertain significance ★ same residue
CDKN2A p.Ala68Leu 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-arg21glu (accessed [today's date]).

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