Is MAPK3 p.Pro328= (c.984C>T) pathogenic?

MAPK3 p.Pro328= (c.984C>T) is classified Likely benign in MAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.00167%, amr).

How common is MAPK3 p.Pro328= (c.984C>T) in the general population?

MAPK3 p.Pro328= (c.984C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

MAPK3 p.Pro328=

c.984C>T · VCV4822226

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.151	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.39, phastCons 1
Overall
CADD	8.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Overall 6.2e-05% 1/1,613,936 alleles · very rare exomes 1/1,461,694 · genomes 0/152,242 · 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: MAPK3
Protein: p.Pro328=
Coding: c.984C>T
MANE Select: NM_002746
Type: single nucleotide variant
Location: chr16:30116927 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 8 PDB
Residue 328: the protein kinase domain; an α-helix

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

Similar variants

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
MAPK3 p.Arg242Gln Uncertain significance ★ ⚠ same type
MAPK3 p.Arg309Gln Uncertain significance ★ ⚠ same type
MAPK3 p.Arg309Gly 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-pro328 (accessed [today's date]).

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