Is MAPK3 p.Gly23= (c.69G>A) pathogenic?

MAPK3 p.Gly23= (c.69G>A) is classified Likely benign in MAPK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-04). Very rare (popmax 8.76e-05%, nfe); Associated with MAPK3-related disorder.

What condition is associated with MAPK3 p.Gly23= (c.69G>A)?

MAPK3 p.Gly23= (c.69G>A) is associated with MAPK3-related disorder (ClinVar).

How common is MAPK3 p.Gly23= (c.69G>A) in the general population?

MAPK3 p.Gly23= (c.69G>A) is very rare (popmax 8.76e-05%, nfe) (gnomAD).

MAPK3 p.Gly23=

c.69G>A · rs2543714902 · VCV3037690

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.76e-05%, nfe)

Conditions

MAPK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Overall
CADD	15.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.76e-05% European (non-Finnish) · 1/1,141,990 alleles

Overall 7.21e-05% 1/1,386,994 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: MAPK3
Protein: p.Gly23=
Coding: c.69G>A
MANE Select: NM_002746
dbSNP: rs2543714902
Type: single nucleotide variant
Location: chr16:30123141 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 8 PDB
Residue 23: the 'disordered' region

Full MAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAPK3-related disorder

Similar variants

MAPK3 p.Tyr42Ter Uncertain significance ★ same condition
MAPK3 c.1017+48G>A Benign same condition
MAPK3 p.Ser159= Likely benign same condition
MAPK3 p.Gly11= Likely benign ★★ same type
MAPK3 p.Pro336= Benign/Likely benign ★★ same type
MAPK3 p.Tyr148Cys Likely pathogenic ★ same type
MAPK3 p.Ala378Asp Uncertain significance ★ ⚠ same type
MAPK3 p.Arg15Ser 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/mapk3-p-gly23 (accessed [today's date]).

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