Is CDKN2A p.Pro11Thr (c.31C>A) pathogenic?

CDKN2A p.Pro11Thr (c.31C>A) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-24). AlphaMissense: likely benign (0.1032); No allele count reported in gnomAD v4.1 (AN 1,604,494); Associated with familial melanoma.

What condition is associated with CDKN2A p.Pro11Thr (c.31C>A)?

CDKN2A p.Pro11Thr (c.31C>A) is associated with familial melanoma (ClinVar).

How common is CDKN2A p.Pro11Thr (c.31C>A) in the general population?

CDKN2A p.Pro11Thr (c.31C>A) is no allele count reported in gnomAD v4.1 (AN 1,604,494) (gnomAD).

How is Familial melanoma inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDKN2A p.Pro11Thr (c.31C>A)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

CDKN2A p.Pro11Thr

c.31C>A · rs1587340371 · VCV1405946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,494)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial melanoma

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.097	GERP -0.99, phastCons 0.056
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	7.159	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,604,494). 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.Pro11Thr
Coding: c.31C>A
MANE Select: NM_000077
dbSNP: rs1587340371
Type: single nucleotide variant
Location: chr9:21974797 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 11: the 'interaction with cdk5rap3 and mdm2' region

Full CDKN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial melanoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDKN2A p.Ile11Ser Uncertain significance ★ same residue
CDKN2A p.Pro11Ala Uncertain significance ★ ⚠ same residue
CDKN2A p.Pro11Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Pro11_Ser12insAlaAlaGlySerSerMetGluPro Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Pro11Arg Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ile11Leu Uncertain significance ★ same residue
CDKN2A p.Ile11Thr Uncertain significance ★ same residue
CDKN2A p.Ile11= Benign ★ 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-pro11thr (accessed [today's date]).

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