Is MAPK3 p.Ser139= (c.417C>T) pathogenic?

MAPK3 p.Ser139= (c.417C>T) is classified Likely benign in MAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Absent from gnomAD v4.1.

How common is MAPK3 p.Ser139= (c.417C>T) in the general population?

MAPK3 p.Ser139= (c.417C>T) is absent from gnomAD v4.1 (gnomAD).

MAPK3 p.Ser139=

c.417C>T · rs1596880352 · VCV736303

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.374	indeterminate
Splicing
SpliceAI	Δ0.43	acceptor loss, 50 bp away · masked 0 · deltas
Pangolin	Δ0.26	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Overall
CADD	13.86	PHRED · no single calibrated threshold — expert panels disagree

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: MAPK3
Protein: p.Ser139=
Coding: c.417C>T
MANE Select: NM_002746
dbSNP: rs1596880352
Type: single nucleotide variant
Location: chr16:30118475 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 8 PDB
Residue 139: 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-ser139 (accessed [today's date]).

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