Is MAPK11 p.Cys162Arg (c.484T>C) pathogenic?

MAPK11 p.Cys162Arg (c.484T>C) is classified Uncertain significance in MAPK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.9933); Very rare (popmax 8.48e-05%, nfe).

How common is MAPK11 p.Cys162Arg (c.484T>C) in the general population?

MAPK11 p.Cys162Arg (c.484T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MAPK11 p.Cys162Arg (c.484T>C)?

AlphaMissense predicts likely pathogenic (score 0.9933) — an in-silico prediction, not a clinical call.

MAPK11 p.Cys162Arg

c.484T>C · VCV3870418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9933	likely pathogenic · top 10% in MAPK11
REVEL	0.46	indeterminate
SaProt	LLR -14.84	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.55 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,341 bp · p 0.0083 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,634 alleles

Overall 6.2e-05% 1/1,611,984 alleles · very rare exomes 1/1,459,770 · genomes 0/152,214 · joint denominator

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.Cys162Arg
Coding: c.484T>C
MANE Select: NM_002751
Type: single nucleotide variant
Location: chr22:50267138 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88 · 4 PDB
Residue 162: the protein kinase domain

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.Arg45Trp Uncertain significance ★ ⚠ same type
MAPK11 p.Asp161Asn 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-cys162arg (accessed [today's date]).

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