Is CDK5RAP2 p.Phe885Leu (c.2655C>G) pathogenic?

CDK5RAP2 p.Phe885Leu (c.2655C>G) is classified Benign/Likely benign in CDK5RAP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.6324); Rare (popmax 0.568%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK5RAP2 p.Phe885Leu (c.2655C>G)?

CDK5RAP2 p.Phe885Leu (c.2655C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK5RAP2 p.Phe885Leu (c.2655C>G) in the general population?

CDK5RAP2 p.Phe885Leu (c.2655C>G) is rare (popmax 0.568%, nfe) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Phe885Leu (c.2655C>G)?

AlphaMissense predicts likely pathogenic (score 0.6324) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Phe885Leu

c.2655C>G · rs112600265 · VCV364762

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.6324 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.568%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6324	likely pathogenic · top 6% in CDK5RAP2
REVEL	0.03	moderately benign-leaning
SaProt	LLR -4.50	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -3, phastCons 0.002
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	4.121	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 0.568% European (non-Finnish) · 6,706/1,180,036 alleles

Filtering AF 0.557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.552%

Overall 0.481% 7,765/1,614,184 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.615%	163
European (non-Finnish)grpmax	0.568%	176
Remaining individualsnot grpmax-eligible	0.466%	215
Admixed American	0.292%	343
South Asian	0.221%	453
Finnishnot grpmax-eligible	0.201%	496
Middle Eastern	0.198%	505
African / African-American	0.0919%	1,088

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe885Leu
Coding: c.2655C>G
MANE Select: NM_018249
dbSNP: rs112600265
Type: single nucleotide variant
Location: chr9:120453594 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB

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-phe885leu (accessed [today's date]).

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