Is CDKN2A p.Ala17Gly (c.50C>G) pathogenic?

CDKN2A p.Ala17Gly (c.50C>G) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.2309); Very rare (popmax 0.000339%, nfe); Associated with Maffucci syndrome.

What condition is associated with CDKN2A p.Ala17Gly (c.50C>G)?

CDKN2A p.Ala17Gly (c.50C>G) is associated with Maffucci syndrome (ClinVar).

How common is CDKN2A p.Ala17Gly (c.50C>G) in the general population?

CDKN2A p.Ala17Gly (c.50C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Maffucci syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDKN2A p.Ala17Gly (c.50C>G)?

AlphaMissense predicts likely benign (score 0.2309) — an in-silico prediction, not a clinical call.

CDKN2A p.Ala17Gly

c.50C>G · rs751809654 · VCV1803801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2309 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Maffucci syndrome

Computational evidence

Protein change
AlphaMissense	0.2309	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -9.04	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 3	GERP -1.4, phastCons 0.25
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	19.16	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,178,774 alleles

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

Overall 0.00255% 37/1,452,958 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0485%	2,060
Remaining individualsnot grpmax-eligible	0.00804%	12,435
European (non-Finnish)grpmax	0.000339%	294,693

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala17Gly
Coding: c.50C>G
MANE Select: NM_000077
dbSNP: rs751809654
Type: single nucleotide variant
Location: chr9:21974778 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 17: an α-helix; the 'interaction with cdk5rap3 and mdm2' region; a UniProt-annotated variant site (in)

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

Disease context

Maffucci syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Maffucci syndrome (Orphanet):

Inheritance: Not applicable
Onset: Childhood

Similar variants

CDKN2A p.Ala17Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro17Ser Uncertain significance ★★ same residue
CDKN2A p.Ala17= Benign/Likely benign ★★ same residue
CDKN2A p.Pro17= Benign/Likely benign ★★ same residue
CDKN2A p.Ala17Asp Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala17Phe Uncertain significance ★ same residue
CDKN2A p.Val106= Conflicting classifications of pathogenicity ★ same condition
CDKN2A c.150+1G>A Likely pathogenic ★★ same type

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-ala17gly (accessed [today's date]).

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