Is MAPK14 p.Leu333= (c.999T>A) pathogenic?

MAPK14 p.Leu333= (c.999T>A) is classified Likely benign in MAPK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). Absent from gnomAD v4.1.

How common is MAPK14 p.Leu333= (c.999T>A) in the general population?

MAPK14 p.Leu333= (c.999T>A) is absent from gnomAD v4.1 (gnomAD).

MAPK14 p.Leu333=

c.999T>A · VCV4103757

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 carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4.8
Overall
CADD	1.629	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: MAPK14
Protein: p.Leu333=
Coding: c.999T>A
MANE Select: NM_139012
Type: single nucleotide variant
Location: chr6:36107612 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 89.91 · 267 PDB

Full MAPK14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK14 c.763-2308A>G Uncertain significance ★ same type
MAPK14 c.763-2312A>G Uncertain significance ★ same type
MAPK14 c.763-2316G>A Uncertain significance ★ same type
MAPK14 c.763-2341C>G Uncertain significance ★ same type
MAPK14 c.763-2356G>A Uncertain significance ★ same type
MAPK14 p.Ala304Val Uncertain significance ★ ⚠ same type
MAPK14 p.Ala41Thr Uncertain significance ★ ⚠ same type
MAPK14 p.Arg10Pro 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/mapk14-p-leu333 (accessed [today's date]).

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