Is CDK5RAP2 p.Ala1358Val (c.4073C>T) pathogenic?

CDK5RAP2 p.Ala1358Val (c.4073C>T) is classified Likely benign in CDK5RAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00878%, sas); Associated with Inborn genetic diseases.

What condition is associated with CDK5RAP2 p.Ala1358Val (c.4073C>T)?

CDK5RAP2 p.Ala1358Val (c.4073C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK5RAP2 p.Ala1358Val (c.4073C>T) in the general population?

CDK5RAP2 p.Ala1358Val (c.4073C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Ala1358Val (c.4073C>T)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Ala1358Val

c.4073C>T · rs540653562 · VCV2488424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.90	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 -1.1	GERP -3.5
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	2.291	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

Grpmax group 0.00878% South Asian · 8/91,078 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00105% 17/1,613,356 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,385
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000678%	147,412

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: CDK5RAP2
Protein: p.Ala1358Val
Coding: c.4073C>T
MANE Select: NM_018249
dbSNP: rs540653562
Type: single nucleotide variant
Location: chr9:120419892 (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 1358: the 'disordered' 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 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
CDK5RAP2 p.Ala905Val 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-ala1358val (accessed [today's date]).

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