Is MAPKAPK2 p.Pro287Ala (c.859C>G) pathogenic?

MAPKAPK2 p.Pro287Ala (c.859C>G) is classified Uncertain significance in MAPKAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.8441); Absent from gnomAD v4.1.

How common is MAPKAPK2 p.Pro287Ala (c.859C>G) in the general population?

MAPKAPK2 p.Pro287Ala (c.859C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAPK2 p.Pro287Ala (c.859C>G)?

AlphaMissense predicts likely pathogenic (score 0.8441) — an in-silico prediction, not a clinical call.

MAPKAPK2 p.Pro287Ala

c.859C>G · VCV4549803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8441 · 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	0.8441	likely pathogenic
REVEL	0.408	indeterminate
SaProt	LLR -14.20	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,966 bp · p 4.2e-07 · regional, not allelic
Overall
CADD	28.3	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.

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: MAPKAPK2
Protein: p.Pro287Ala
Coding: c.859C>G
MANE Select: NM_032960
Type: single nucleotide variant
Location: chr1:206731229 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 287: the protein kinase domain

Full MAPKAPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAPK2 p.Pro17= Likely benign ★★ same type
MAPKAPK2 p.Thr66= Benign ★★ same type
MAPKAPK2 p.Ala111Val Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala33Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala378Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala390Thr Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg110Trp Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg119Gln 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/mapkapk2-p-pro287ala (accessed [today's date]).

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