Is CDK5RAP2 p.Ala696= (c.2088G>A) pathogenic?

CDK5RAP2 p.Ala696= (c.2088G>A) is classified Likely benign in CDK5RAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). Ultra-rare (popmax 0.024%, afr).

How common is CDK5RAP2 p.Ala696= (c.2088G>A) in the general population?

CDK5RAP2 p.Ala696= (c.2088G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

CDK5RAP2 p.Ala696=

c.2088G>A · rs374805157 · VCV761553

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -4.3
Overall
CADD	5.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,030 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00545% 88/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
African / African-Americangrpmax	0.024%	4,168
East Asian	0.0201%	4,986
South Asian	0.00549%	18,216
Admixed American	0.00167%	60,022
European (non-Finnish)	0.00144%	69,412

Remaining individuals 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.Ala696=
Coding: c.2088G>A
MANE Select: NM_018249
dbSNP: rs374805157
Type: single nucleotide variant
Location: chr9:120467878 (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

Similar variants

CDK5RAP2 p.Ala696Val Uncertain significance ★★ ⚠ same residue
CDK5RAP2 p.Ala696Pro Uncertain significance ★ ⚠ same residue
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

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-ala696 (accessed [today's date]).

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