Is MAPKAPK3 p.Pro268Arg (c.803C>G) pathogenic?

MAPKAPK3 p.Pro268Arg (c.803C>G) is classified Uncertain significance in MAPKAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: ambiguous (0.4846); Absent from gnomAD v4.1.

How common is MAPKAPK3 p.Pro268Arg (c.803C>G) in the general population?

MAPKAPK3 p.Pro268Arg (c.803C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAPK3 p.Pro268Arg (c.803C>G)?

AlphaMissense predicts ambiguous (score 0.4846) — an in-silico prediction, not a clinical call.

MAPKAPK3 p.Pro268Arg

c.803C>G · rs2033293275 · VCV2087428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4846 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4846	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -12.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,880 bp · p 0.058 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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: MAPKAPK3
Protein: p.Pro268Arg
Coding: c.803C>G
MANE Select: NM_001243925
dbSNP: rs2033293275
Type: single nucleotide variant
Location: chr3:50646238 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.10 · 5 PDB
Residue 268: the protein kinase domain; a turn

Full MAPKAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAPK3 p.Pro268Ala Uncertain significance ★ ⚠ same residue
MAPKAPK3 p.Ala181Ser Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg112His Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg148Gln Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg148Trp Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg259Cys Uncertain significance ★★ same type
MAPKAPK3 p.Arg282Cys Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg282His 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/mapkapk3-p-pro268arg (accessed [today's date]).

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