Is CDK5RAP2 p.Arg1607Ser (c.4821G>C) pathogenic?

CDK5RAP2 p.Arg1607Ser (c.4821G>C) is classified Benign/Likely benign in CDK5RAP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.3182); Low-frequency (popmax 4.9%, afr).

How common is CDK5RAP2 p.Arg1607Ser (c.4821G>C) in the general population?

CDK5RAP2 p.Arg1607Ser (c.4821G>C) is low-frequency (popmax 4.9%, afr) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Arg1607Ser (c.4821G>C)?

AlphaMissense predicts likely benign (score 0.3182) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Arg1607Ser

c.4821G>C · rs16909747 · VCV158154

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.3182 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.9%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3182	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.11	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 -0.3, phastCons 0.96
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	20.2	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 4.9% African / African-American · 3,678/75,030 alleles

Filtering AF 4.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.72%

Overall 0.266% 4,286/1,614,042 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.9%	20
Remaining individualsnot grpmax-eligible	0.379%	264
Admixed American	0.357%	280
Middle Eastern	0.198%	505
European (non-Finnish)	0.0114%	8,806
South Asian	0.011%	9,109
Finnishnot grpmax-eligible	0.00156%	63,898

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.Arg1607Ser
Coding: c.4821G>C
MANE Select: NM_018249
dbSNP: rs16909747
Type: single nucleotide variant
Location: chr9:120407154 (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 1607: a UniProt-annotated variant site (in)

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

Similar variants

CDK5RAP2 c.4005-1G>A Pathogenic ★★ same type
CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same type
CDK5RAP2 p.Arg427Ter Pathogenic ★★ same type
CDK5RAP2 p.Gln1301Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Gln1474Ter Pathogenic ★★ same type

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-arg1607ser (accessed [today's date]).

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