Is MAPKAPK3 p.Pro302Ala (c.904C>G) pathogenic?

MAPKAPK3 p.Pro302Ala (c.904C>G) is classified Uncertain significance in MAPKAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1331); Absent from gnomAD v4.1.

How common is MAPKAPK3 p.Pro302Ala (c.904C>G) in the general population?

MAPKAPK3 p.Pro302Ala (c.904C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAPK3 p.Pro302Ala (c.904C>G)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

MAPKAPK3 p.Pro302Ala

c.904C>G · VCV3648335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.455	indeterminate
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,880 bp · p 0.058 · regional, not allelic
Overall
CADD	25.5	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.Pro302Ala
Coding: c.904C>G
MANE Select: NM_001243925
Type: single nucleotide variant
Location: chr3:50646814 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.10 · 5 PDB
Residue 302: the protein kinase domain; an α-helix

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

Similar variants

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
MAPKAPK3 p.Arg319Gln 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-pro302ala (accessed [today's date]).

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