Is CDK2AP1 p.Tyr63= (c.189C>T) pathogenic?

CDK2AP1 p.Tyr63= (c.189C>T) is classified Benign in CDK2AP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele.

CDK2AP1 p.Tyr63=

Q: How common is CDK2AP1 p.Tyr63= (c.189C>T) in the general population?

CDK2AP1 p.Tyr63= (c.189C>T) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.189C>T · rs76783415 · VCV776771

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -7.7	GERP -3.8
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,571/74,994 alleles

Filtering AF 9.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.83%

Overall 0.54% 8,719/1,614,074 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Remaining individualsnot grpmax-eligible	0.651%	154
Admixed American	0.568%	176
Middle Eastern	0.396%	253
European (non-Finnish)	0.031%	3,224
South Asian	0.00878%	11,385
Finnishnot grpmax-eligible	0.00312%	32,018

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.Tyr63=
Coding: c.189C>T
MANE Select: NM_004642
dbSNP: rs76783415
Type: single nucleotide variant
Location: chr12:123265287 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 1 PDB
Residue 63: an α-helix

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

Similar variants

CDK2AP1 p.Gln57= Benign ★★ same type
CDK2AP1 p.Ala30Ser Uncertain significance ★ ⚠ 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-tyr63 (accessed [today's date]).

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