Is MAPK9 p.Asp7Glu (c.21C>G) pathogenic?

MAPK9 p.Asp7Glu (c.21C>G) is classified Uncertain significance in MAPK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0938); Very rare (popmax 0.00667%, afr).

How common is MAPK9 p.Asp7Glu (c.21C>G) in the general population?

MAPK9 p.Asp7Glu (c.21C>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about MAPK9 p.Asp7Glu (c.21C>G)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

MAPK9 p.Asp7Glu

c.21C>G · VCV4549796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.2, phastCons 0.003
Regional constraint	o/e 0.95	unconstrained · MANE · 96 bp · p 0.74 · regional, not allelic
Overall
CADD	6.951	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 0.00667% African / African-American · 5/74,938 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,613,978 alleles · very rare

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: MAPK9
Protein: p.Asp7Glu
Coding: c.21C>G
MANE Select: NM_002752
Type: single nucleotide variant
Location: chr5:180280541 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 5 PDB
Residue 7: a turn

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-asp7glu (accessed [today's date]).

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