Is CDK5RAP2 p.Ser140Pro (c.418T>C) pathogenic?

CDK5RAP2 p.Ser140Pro (c.418T>C) is classified Uncertain significance in CDK5RAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). AlphaMissense: likely benign (0.136); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDK5RAP2 p.Ser140Pro (c.418T>C)?

CDK5RAP2 p.Ser140Pro (c.418T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDK5RAP2 p.Ser140Pro (c.418T>C) in the general population?

CDK5RAP2 p.Ser140Pro (c.418T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK5RAP2 p.Ser140Pro (c.418T>C)?

AlphaMissense predicts likely benign (score 0.136) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Ser140Pro

c.418T>C · rs2539696667 · VCV2549341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.136 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.136	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	23.7	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.Ser140Pro
Coding: c.418T>C
MANE Select: NM_018249
dbSNP: rs2539696667
Type: single nucleotide variant
Location: chr9:120539130 (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 140: the 'interaction with nckap5l' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK5RAP2 p.Ser140Cys Uncertain significance ★ ⚠ same residue
CDK5RAP2 c.1727+6C>G Uncertain significance ★★ same condition
CDK5RAP2 p.Ala181Ser Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala235Thr Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala326Ser Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala358Thr Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala382Val Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala764Pro Uncertain significance ★★ ⚠ 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-ser140pro (accessed [today's date]).

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