Is MAPK11 p.Ile362Val (c.1084A>G) pathogenic?

MAPK11 p.Ile362Val (c.1084A>G) is classified Uncertain significance in MAPK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0919%, amr).

How common is MAPK11 p.Ile362Val (c.1084A>G) in the general population?

MAPK11 p.Ile362Val (c.1084A>G) is ultra-rare (popmax 0.0919%, amr) (gnomAD).

What do computational predictors say about MAPK11 p.Ile362Val (c.1084A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

MAPK11 p.Ile362Val

c.1084A>G · VCV4103718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0919%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -4.96	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 -1.5	GERP -1.2
Regional constraint	o/e 0.88	unconstrained · MANE · 5,341 bp · p 0.0083 · regional, not allelic
Overall
CADD	8.468	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 0.0919% Admixed American · 55/59,816 alleles

Filtering AF 0.0725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0655%

Overall 0.0116% 187/1,611,786 alleles · ultra-rare exomes 147/1,459,584 · genomes 40/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0919%	1,088
Remaining individualsnot grpmax-eligible	0.0112%	8,916
European (non-Finnish)	0.0105%	9,511
Finnishnot grpmax-eligible	0.00158%	63,424

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.Ile362Val
Coding: c.1084A>G
MANE Select: NM_002751
Type: single nucleotide variant
Location: chr22:50264959 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88 · 4 PDB
Residue 362: the 'disordered' region

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-ile362val (accessed [today's date]).

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