Is MAPK14 p.Pro352Thr (c.1054C>A) pathogenic?

MAPK14 p.Pro352Thr (c.1054C>A) is classified Uncertain significance in MAPK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.066); Absent from gnomAD v4.1.

How common is MAPK14 p.Pro352Thr (c.1054C>A) in the general population?

MAPK14 p.Pro352Thr (c.1054C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK14 p.Pro352Thr (c.1054C>A)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

MAPK14 p.Pro352Thr

c.1054C>A · VCV4549715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -7.96	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 80 kb · p 7.2e-32 · regional, not allelic
Overall
CADD	20.7	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

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.Pro352Thr
Coding: c.1054C>A
MANE Select: NM_139012
Type: single nucleotide variant
Location: chr6:36108418 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 89.91 · 267 PDB
Residue 352: an α-helix

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-pro352thr (accessed [today's date]).

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