Is CDKN2A p.Ala35= (c.105A>C) pathogenic?

CDKN2A p.Ala35= (c.105A>C) is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-19). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala35= (c.105A>C)?

CDKN2A p.Ala35= (c.105A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Ala35= (c.105A>C) in the general population?

CDKN2A p.Ala35= (c.105A>C) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Ala35=

c.105A>C · rs2131148479 · VCV1779683

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -2.1
Overall
CADD	10.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN2A
Protein: p.Ala35=
Coding: c.105A>C
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2131148479
Type: single nucleotide variant
Location: chr9:21994227 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 35: a UniProt-annotated variant site (in cmm2; also found in a biliary tract tumor and a patient with uveal melanoma; partial loss of cdk4 binding); a UniProt-annotated variant site (in cmm2); a UniProt-annotated variant site (in cmm2; loss of cdk4 binding); 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.Gly35Arg Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly35Glu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly35Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly35= Likely benign ★★ same residue
CDKN2A p.Ala35Ser Uncertain significance ★ same residue
CDKN2A p.Gly35Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Ala35Pro Uncertain significance ★ same residue
CDKN2A p.Ala35Val 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-ala35 (accessed [today's date]).

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