Is MAPK9 p.Lys290Arg (c.869A>G) pathogenic?

MAPK9 p.Lys290Arg (c.869A>G) is classified Uncertain significance in MAPK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.096); Absent from gnomAD v4.1.

How common is MAPK9 p.Lys290Arg (c.869A>G) in the general population?

MAPK9 p.Lys290Arg (c.869A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK9 p.Lys290Arg (c.869A>G)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

MAPK9 p.Lys290Arg

c.869A>G · VCV4103862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 0.00097 · regional, not allelic
Overall
CADD	25.8	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: MAPK9
Protein: p.Lys290Arg
Coding: c.869A>G
MANE Select: NM_002752
Type: single nucleotide variant
Location: chr5:180242575 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 5 PDB
Residue 290: the protein kinase domain; an α-helix

Full MAPK9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK9 c.617-399G>A Uncertain significance ★ same type
MAPK9 p.Ala246Val Uncertain significance ★ ⚠ same type
MAPK9 p.Arg174Gly Uncertain significance ★ ⚠ same type
MAPK9 p.Arg25Cys Uncertain significance ★ ⚠ same type
MAPK9 p.Arg25His Uncertain significance ★ ⚠ same type
MAPK9 p.Arg424Pro Uncertain significance ★ ⚠ same type
MAPK9 p.Asn262Lys Uncertain significance ★ ⚠ same type
MAPK9 p.Asn394Ser 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/mapk9-p-lys290arg (accessed [today's date]).

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