Is MAP2K2 p.Phe57= (c.171T>C) pathogenic?

MAP2K2 p.Phe57= (c.171T>C) is classified Likely benign in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-27). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Phe57= (c.171T>C)?

MAP2K2 p.Phe57= (c.171T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K2 p.Phe57= (c.171T>C) in the general population?

MAP2K2 p.Phe57= (c.171T>C) is absent from gnomAD v4.1 (gnomAD).

MAP2K2 p.Phe57=

c.171T>C · rs1057519910 · VCV1778739

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP -0.72, phastCons 1
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

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: MAP2K2
Protein: p.Phe57=
Coding: c.171T>C
MANE Select: NM_030662
dbSNP: rs1057519910
Type: single nucleotide variant
Location: chr19:4117551 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 57: a UniProt-annotated variant site (in cfc4)

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

Similar variants

MAP2K2 p.Phe57Cys Pathogenic ★★★ same residue
MAP2K2 p.Phe57Val Pathogenic ★★★ same residue
MAP2K2 p.Phe57Leu Pathogenic/Likely pathogenic ★★ same residue
MAP2K2 p.Phe57Ile Uncertain significance ★ ⚠ same residue
MAP2K2 p.Phe57Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP2K2 p.Gly132Asp Pathogenic/Likely pathogenic ★★ same condition
MAP2K2 c.450+5G>A Uncertain significance ★★ same condition
MAP2K2 p.Ala355Val Uncertain significance ★★ ⚠ 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-phe57 (accessed [today's date]).

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