Is CDK2AP1 p.Ala30Ser (c.88G>T) pathogenic?

CDK2AP1 p.Ala30Ser (c.88G>T) is classified Uncertain significance in CDK2AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.0888); Very rare (popmax 6.2e-05%).

How common is CDK2AP1 p.Ala30Ser (c.88G>T) in the general population?

CDK2AP1 p.Ala30Ser (c.88G>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about CDK2AP1 p.Ala30Ser (c.88G>T)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CDK2AP1 p.Ala30Ser

c.88G>T · VCV4224553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 4,386 bp · p 0.26 · regional, not allelic
Overall
CADD	22.3	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 6.2e-05%

Overall 6.2e-05% 1/1,613,172 alleles · very rare exomes 1/1,460,966 · genomes 0/152,206 · joint denominator

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: CDK2AP1
Protein: p.Ala30Ser
Coding: c.88G>T
MANE Select: NM_004642
Type: single nucleotide variant
Location: chr12:123267250 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 1 PDB

Full CDK2AP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK2AP1 p.Gln57= Benign ★★ same type
CDK2AP1 p.Tyr63= Benign ★★ same type
CDK2AP1 p.Arg111Trp Uncertain significance ★ ⚠ same type
CDK2AP1 p.Gly43Arg Uncertain significance ★ ⚠ same type
CDK2AP1 p.Leu7Phe Uncertain significance ★ ⚠ same type
CDK2AP1 p.Met11Val Uncertain significance ★ ⚠ same type
CDK2AP1 p.Pro25His Uncertain significance ★ ⚠ same type
CDK2AP1 p.Pro45Leu Uncertain significance ★ ⚠ 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/cdk2ap1-p-ala30ser (accessed [today's date]).

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