Is CDKN2A p.Tyr44= (c.132C>T) pathogenic?

CDKN2A p.Tyr44= (c.132C>T) is classified Benign/Likely benign in CDKN2A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-04). Very rare (popmax 0.000339%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Tyr44= (c.132C>T)?

CDKN2A p.Tyr44= (c.132C>T) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Tyr44= (c.132C>T) in the general population?

CDKN2A p.Tyr44= (c.132C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

CDKN2A p.Tyr44=

c.132C>T · rs1554656253 · VCV483351

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.4	GERP -4.1
Overall
CADD	3.295	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,968 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,694 alleles · very rare exomes 4/1,461,440 · genomes 0/152,254 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN2A
Protein: p.Tyr44=
Coding: c.132C>T
MANE Select: NM_000077
dbSNP: rs1554656253
Type: single nucleotide variant
Location: chr9:21974696 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 44: a β-strand; 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

Also linked: melanoma-pancreatic cancer syndrome familial melanoma

Similar variants

CDKN2A p.Ala44Val Uncertain significance ★★ same residue
CDKN2A p.Ala44Ser Uncertain significance ★ same residue
CDKN2A p.Ala44Thr Uncertain significance ★ same residue
CDKN2A p.Tyr44Cys Uncertain significance ★ same residue
CDKN2A p.Ala44= Likely benign ★ same residue
CDKN2A p.Tyr44Ter Pathogenic ★★ same residue
CDKN2A p.Tyr44fs Pathogenic ★ same residue
CDKN2A p.Tyr44_Gly45insTyr 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-tyr44 (accessed [today's date]).

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