Is MAPK1 p.Arg50Gln (c.149G>A) pathogenic?

MAPK1 p.Arg50Gln (c.149G>A) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: ambiguous (0.4924); Very rare (popmax 0.00017%, nfe).

How common is MAPK1 p.Arg50Gln (c.149G>A) in the general population?

MAPK1 p.Arg50Gln (c.149G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MAPK1 p.Arg50Gln (c.149G>A)?

AlphaMissense predicts ambiguous (score 0.4924) — an in-silico prediction, not a clinical call.

MAPK1 p.Arg50Gln

c.149G>A · VCV3899570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4924	ambiguous
REVEL	0.319	indeterminate
SaProt	LLR -7.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 60 kb · p 0.89 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,806 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,498 alleles · very rare exomes 2/1,461,372 · genomes 0/152,126 · 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: MAPK1
Protein: p.Arg50Gln
Coding: c.149G>A
MANE Select: NM_002745
Type: single nucleotide variant
Location: chr22:21807817 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 50: the protein kinase domain; a β-strand

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-arg50gln (accessed [today's date]).

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