Is CDK5RAP2 p.Ser1083Arg (c.3247A>C) pathogenic?

CDK5RAP2 p.Ser1083Arg (c.3247A>C) is classified Likely benign in CDK5RAP2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.2773); Absent from gnomAD v4.1; Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with CDK5RAP2 p.Ser1083Arg (c.3247A>C)?

CDK5RAP2 p.Ser1083Arg (c.3247A>C) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is CDK5RAP2 p.Ser1083Arg (c.3247A>C) in the general population?

CDK5RAP2 p.Ser1083Arg (c.3247A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK5RAP2 p.Ser1083Arg (c.3247A>C)?

AlphaMissense predicts likely benign (score 0.2773) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Ser1083Arg

c.3247A>C · rs2539036849 · VCV2681712

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2773 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
AlphaMissense	0.2773	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -0.89, phastCons 0.5
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	17.63	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: CDK5RAP2
Protein: p.Ser1083Arg
Coding: c.3247A>C
MANE Select: NM_018249
dbSNP: rs2539036849
Type: single nucleotide variant
Location: chr9:120439874 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB
Residue 1083: the 'interaction with mapre1' region

Full CDK5RAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same condition
CDK5RAP2 p.Arg150Ter Pathogenic ★ same condition
CDK5RAP2 c.5452-8C>T Conflicting classifications of pathogenicity ★ same condition
CDK5RAP2 p.Glu225Ter Likely pathogenic same condition
CDK5RAP2 p.Ser1608Asn Uncertain significance ⚠ same condition
CDK5RAP2 p.Gln593= Likely benign same condition
CDK5RAP2 p.His1182= Likely benign same condition
CDK5RAP2 p.Pro1587= Likely benign 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/cdk5rap2-p-ser1083arg (accessed [today's date]).

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