Is CDKN2A p.Ala30Glu (c.89C>A) pathogenic?

CDKN2A p.Ala30Glu (c.89C>A) is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-28). AlphaMissense: likely benign (0.0953); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala30Glu (c.89C>A)?

CDKN2A p.Ala30Glu (c.89C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Ala30Glu (c.89C>A) in the general population?

CDKN2A p.Ala30Glu (c.89C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Ala30Glu (c.89C>A)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

CDKN2A p.Ala30Glu

c.89C>A · VCV3489674

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP 0.089
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	13.23	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala30Glu
Coding: c.89C>A
MANE Select: NM_000077
Type: single nucleotide variant
Location: chr9:21974739 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 30: 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.Ala30Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Leu30Phe Uncertain significance ★★ same residue
CDKN2A p.Leu30= Benign/Likely benign ★★ same residue
CDKN2A p.Ala30Gly Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala30Thr Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala30= Likely benign ★ same residue
CDKN2A c.150+2T>G Likely 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-ala30glu (accessed [today's date]).

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