Is MAP2K2 p.Gly152= (c.456C>T) pathogenic?

MAP2K2 p.Gly152= (c.456C>T) is classified Benign/Likely benign in MAP2K2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.016%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Gly152= (c.456C>T)?

MAP2K2 p.Gly152= (c.456C>T) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is MAP2K2 p.Gly152= (c.456C>T) in the general population?

MAP2K2 p.Gly152= (c.456C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

MAP2K2 p.Gly152=

c.456C>T · rs143106439 · VCV512068

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

Cardiovascular phenotype

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 -5.4	GERP -3.5
Overall
CADD	3.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,808 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00569% 91/1,600,698 alleles · ultra-rare exomes 84/1,448,490 · genomes 7/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,234
Admixed American	0.00689%	14,507
South Asian	0.00675%	14,817
East Asian	0.00675%	14,825
European (non-Finnish)	0.00528%	18,948
Finnishnot grpmax-eligible	0.00488%	20,479
Remaining individualsnot grpmax-eligible	0.00161%	62,012

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: MAP2K2
Protein: p.Gly152=
Coding: c.456C>T
MANE Select: NM_030662
dbSNP: rs143106439
Type: single nucleotide variant
Location: chr19:4102448 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 152: the protein kinase domain

Full MAP2K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RASopathy

Similar variants

MAP2K2 p.Gly152Asp Uncertain significance ★★ ⚠ same residue
MAP2K2 p.Gly152Ser Uncertain significance ★★ ⚠ same residue
MAP2K2 p.Gly152Cys Uncertain significance ★ ⚠ same residue
MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
MAP2K2 p.Tyr134His Pathogenic ★★★ same condition

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/map2k2-p-gly152 (accessed [today's date]).

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