Is CDK11A p.Val485Phe (c.1453G>T) pathogenic?

CDK11A p.Val485Phe (c.1453G>T) is classified Uncertain significance in CDK11A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely pathogenic (0.9676); Absent from gnomAD v4.1.

How common is CDK11A p.Val485Phe (c.1453G>T) in the general population?

CDK11A p.Val485Phe (c.1453G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK11A p.Val485Phe (c.1453G>T)?

AlphaMissense predicts likely pathogenic (score 0.9676) — an in-silico prediction, not a clinical call.

CDK11A p.Val485Phe

c.1453G>T · VCV4224163

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9676 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9676	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -14.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	phastCons 0.64
Regional constraint	o/e 0.90	unconstrained · MANE · 4,581 bp · p 0.038 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V488F vs ClinVar V485F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK11A
Protein: p.Val485Phe
Coding: c.1453G>T
MANE Select: NM_024011
Type: single nucleotide variant
Location: chr1:1704909 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.94
Residue 488 UniProt numbering: the protein kinase domain

Full CDK11A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK11A p.Val485Ile Uncertain significance ★ ⚠ same residue
CDK11A p.Arg247Gln Uncertain significance ★★ ⚠ same type
CDK11A p.Ala196Val Uncertain significance ★ ⚠ same type
CDK11A p.Ala558Thr Uncertain significance ★ ⚠ same type
CDK11A p.Ala590Thr Uncertain significance ★ same type
CDK11A p.Ala597Val Uncertain significance ★ ⚠ same type
CDK11A p.Arg131Cys Uncertain significance ★ ⚠ same type
CDK11A p.Arg132Gln 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/cdk11a-p-val485phe (accessed [today's date]).

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