Is MAP2K1 p.Arg201His (c.602G>A) pathogenic?

MAP2K1 p.Arg201His (c.602G>A) is classified Uncertain significance in MAP2K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: ambiguous (0.4221); Very rare (popmax 0.000424%, nfe).

How common is MAP2K1 p.Arg201His (c.602G>A) in the general population?

MAP2K1 p.Arg201His (c.602G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MAP2K1 p.Arg201His (c.602G>A)?

AlphaMissense predicts ambiguous (score 0.4221) — an in-silico prediction, not a clinical call.

MAP2K1 p.Arg201His

c.602G>A · rs2140667506 · VCV1810126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4221 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4221	ambiguous
REVEL	0.563	indeterminate
SaProt	LLR -6.72	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP -0.028, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 94 kb · p 1.7e-15 · regional, not allelic
Overall
CADD	29.6	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 0.000424% European (non-Finnish) · 5/1,179,920 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,406 alleles · very rare exomes 5/1,461,156 · genomes 0/152,250 · 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: MAP2K1
Protein: p.Arg201His
Coding: c.602G>A
MANE Select: NM_002755
dbSNP: rs2140667506
Type: single nucleotide variant
Location: chr15:66481788 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.05 · 99 PDB
Residue 201: the protein kinase domain; a turn

Full MAP2K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K1 p.Arg201= Likely benign ★ same residue
MAP2K1 p.Arg108Leu Likely pathogenic ★★★ same type
MAP2K1 p.Asn122Asp Pathogenic ★★★ ⚠ same type
MAP2K1 p.Asp67Asn Pathogenic ★★★ same type
MAP2K1 p.Glu203Gly Pathogenic ★★★ same type
MAP2K1 p.Leu42Arg Likely pathogenic ★★★ same type
MAP2K1 p.Leu42Phe Pathogenic ★★★ same type
MAP2K1 p.Leu92Arg Pathogenic ★★★ 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/map2k1-p-arg201his (accessed [today's date]).

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