Is CDK5 p.His27Gln (c.81T>G) pathogenic?

CDK5 p.His27Gln (c.81T>G) is classified Uncertain significance in CDK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1451); Ultra-rare (popmax 0.0673%, nfe).

How common is CDK5 p.His27Gln (c.81T>G) in the general population?

CDK5 p.His27Gln (c.81T>G) is ultra-rare (popmax 0.0673%, nfe) (gnomAD).

What do computational predictors say about CDK5 p.His27Gln (c.81T>G)?

AlphaMissense predicts likely benign (score 0.1451) — an in-silico prediction, not a clinical call.

CDK5 p.His27Gln

c.81T>G · VCV4831192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1451 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0673%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1451	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -5.23	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 1.4	GERP 0.93, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 1,256 bp · p 3.2e-10 · regional, not allelic
Overall
CADD	16.54	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 0.0673% European (non-Finnish) · 787/1,169,986 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0618%

Overall 0.0538% 863/1,602,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0673%	1,487
Remaining individualsnot grpmax-eligible	0.0579%	1,726
Middle Eastern	0.0332%	3,016
African / African-American	0.0227%	4,400
South Asian	0.0132%	7,568
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,848
East Asian	0.00893%	11,199
Admixed American	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	63,944

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: CDK5
Protein: p.His27Gln
Coding: c.81T>G
MANE Select: NM_004935
Type: single nucleotide variant
Location: chr7:151057117 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 91.83 · 12 PDB
Residue 27: the protein kinase domain

Full CDK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK5 p.Met230Val Uncertain significance ★★ ⚠ same type
CDK5 c.194+12G>A Benign/Likely benign ★★ same type
CDK5 c.312+3G>A Benign ★★ same type
CDK5 c.408+9T>C Likely benign ★★ same type
CDK5 c.483+11A>C Benign ★★ same type
CDK5 p.Pro240= Likely benign ★★ same type
CDK5 p.Ser72= Benign/Likely benign ★★ same type
CDK5 p.Arg50Gln Likely 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/cdk5-p-his27gln (accessed [today's date]).

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