Is MAPK1 p.Pro152Ser (c.454C>T) pathogenic?

MAPK1 p.Pro152Ser (c.454C>T) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1.

How common is MAPK1 p.Pro152Ser (c.454C>T) in the general population?

MAPK1 p.Pro152Ser (c.454C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK1 p.Pro152Ser (c.454C>T)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

MAPK1 p.Pro152Ser

c.454C>T · VCV3370631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 9% in MAPK1
REVEL	0.696	pathogenic-leaning
SaProt	LLR -14.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 17 kb · p 2.1e-19 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: MAPK1
Protein: p.Pro152Ser
Coding: c.454C>T
MANE Select: NM_002745
Type: single nucleotide variant
Location: chr22:21805888 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 152: the protein kinase domain; an α-helix

Full MAPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK1 p.Ala174Val Pathogenic ★★ ⚠ same type
MAPK1 p.Arg135Thr Likely pathogenic ★★ same type
MAPK1 p.Asp318Asn Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.Asp318Gly Pathogenic ★★ same type
MAPK1 p.Glu322Gln Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.His80Tyr Pathogenic ★★ same type
MAPK1 p.Asn27Asp Uncertain significance ★★ ⚠ same type
MAPK1 p.Ala325= Likely benign ★★ 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/mapk1-p-pro152ser (accessed [today's date]).

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