Is MAPK11 p.Arg45Trp (c.133C>T) pathogenic?

MAPK11 p.Arg45Trp (c.133C>T) is classified Uncertain significance in MAPK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.1806); Very rare (popmax 0.0014%, afr).

How common is MAPK11 p.Arg45Trp (c.133C>T) in the general population?

MAPK11 p.Arg45Trp (c.133C>T) is very rare (popmax 0.0014%, afr) (gnomAD).

What do computational predictors say about MAPK11 p.Arg45Trp (c.133C>T)?

AlphaMissense predicts likely benign (score 0.1806) — an in-silico prediction, not a clinical call.

MAPK11 p.Arg45Trp

c.133C>T · rs751375132 · VCV2534863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0014%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1806	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.075, phastCons 0.14
Regional constraint	o/e 0.88	unconstrained · MANE · 5,341 bp · p 0.0083 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0014% African / African-American · 1/71,646 alleles

Overall 0.000127% 2/1,574,466 alleles · very rare exomes 2/1,422,156 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0014%	71,646
European (non-Finnish)	8.6e-05%	1,162,960

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: MAPK11
Protein: p.Arg45Trp
Coding: c.133C>T
MANE Select: NM_002751
dbSNP: rs751375132
Type: single nucleotide variant
Location: chr22:50267933 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88 · 4 PDB
Residue 45: the protein kinase domain; a turn

Full MAPK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK11 c.611-7C>T Benign ★★ same type
MAPK11 p.Ala121Ser Uncertain significance ★ ⚠ same type
MAPK11 p.Ala184Thr Uncertain significance ★ ⚠ same type
MAPK11 p.Ala304Ser Uncertain significance ★ ⚠ same type
MAPK11 p.Arg189Gln Uncertain significance ★ ⚠ same type
MAPK11 p.Arg332His Uncertain significance ★ ⚠ same type
MAPK11 p.Asp161Asn Uncertain significance ★ ⚠ same type
MAPK11 p.Asp176Glu 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/mapk11-p-arg45trp (accessed [today's date]).

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