Is CDKN2A p.Asp116Glu (c.348C>A) pathogenic?

CDKN2A p.Asp116Glu (c.348C>A) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-14). AlphaMissense: likely benign (0.319); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Asp116Glu (c.348C>A)?

CDKN2A p.Asp116Glu (c.348C>A) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Asp116Glu (c.348C>A) in the general population?

CDKN2A p.Asp116Glu (c.348C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Asp116Glu (c.348C>A)?

AlphaMissense predicts likely benign (score 0.319) — an in-silico prediction, not a clinical call.

CDKN2A p.Asp116Glu

c.348C>A · rs995881157 · VCV489867

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.319 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,380)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.319	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -7.63	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 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	23.9	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 1,608,380). 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.Asp116Glu
Coding: c.348C>A
MANE Select: NM_000077
dbSNP: rs995881157
Type: single nucleotide variant
Location: chr9:21971011 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 116: an α-helix; a UniProt-annotated variant site (in); the 'disordered' 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: familial melanoma

Similar variants

CDKN2A p.Asp116Tyr 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
CDKN2A c.151-1G>C Pathogenic ★★ same condition
CDKN2A c.151-1G>T Pathogenic/Likely pathogenic ★★ same condition
CDKN2A c.151-2A>G Pathogenic/Likely pathogenic ★★ same condition
CDKN2A c.193+1G>A Pathogenic/Likely 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-asp116glu (accessed [today's date]).

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