Is CDKN2A p.Asp153Asn (c.457G>A) pathogenic?

CDKN2A p.Asp153Asn (c.457G>A) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1258); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Asp153Asn (c.457G>A)?

CDKN2A p.Asp153Asn (c.457G>A) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Asp153Asn (c.457G>A) in the general population?

CDKN2A p.Asp153Asn (c.457G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Asp153Asn (c.457G>A)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

CDKN2A p.Asp153Asn

c.457G>A · rs45476696 · VCV532292

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.522	indeterminate
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.73	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.69	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.6	GERP 0.87, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	25.5	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.Asp153Asn
Coding: c.457G>A
MANE Select: NM_000077
dbSNP: rs45476696
Type: single nucleotide variant
Location: chr9:21970902 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 153: a β-strand

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: familial melanoma

Similar variants

CDKN2A p.Asp153Tyr Pathogenic/Likely pathogenic ★★ ⚠ same residue
CDKN2A p.Asp153His Uncertain significance ★★ ⚠ same residue
CDKN2A p.Asp153Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Asp153= Conflicting classifications of pathogenicity ★ same residue
CDKN2A p.Asp153Gly Uncertain significance ★ ⚠ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A 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-asp153asn (accessed [today's date]).

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