Is CDK5RAP2 p.Arg144Gln (c.431G>A) pathogenic?

CDK5RAP2 p.Arg144Gln (c.431G>A) is classified Uncertain significance in CDK5RAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-07). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.029%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDK5RAP2 p.Arg144Gln (c.431G>A)?

CDK5RAP2 p.Arg144Gln (c.431G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDK5RAP2 p.Arg144Gln (c.431G>A) in the general population?

CDK5RAP2 p.Arg144Gln (c.431G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Arg144Gln (c.431G>A)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Arg144Gln

c.431G>A · rs569356580 · VCV2419562

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.28	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 0.86	GERP 0.21, phastCons 0.27
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	21.5	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 0.029% East Asian · 13/44,892 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00167% 27/1,613,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,453
Remaining individualsnot grpmax-eligible	0.008%	12,493
Finnishnot grpmax-eligible	0.00312%	32,008
European (non-Finnish)	0.000593%	168,561

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.Arg144Gln
Coding: c.431G>A
MANE Select: NM_018249
dbSNP: rs569356580
Type: single nucleotide variant
Location: chr9:120539117 (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 144: 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.Arg144Trp Uncertain significance ★★ ⚠ same residue
CDK5RAP2 p.Arg144= Likely benign ★★ 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

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-arg144gln (accessed [today's date]).

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