Is MAP2K2 p.Leu78= (c.232C>T) pathogenic?

MAP2K2 p.Leu78= (c.232C>T) is classified Likely benign in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Leu78= (c.232C>T)?

MAP2K2 p.Leu78= (c.232C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K2 p.Leu78= (c.232C>T) in the general population?

MAP2K2 p.Leu78= (c.232C>T) is absent from gnomAD v4.1 (gnomAD).

MAP2K2 p.Leu78=

c.232C>T · rs2041238210 · VCV2565285

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	all four deltas below 0.2 · G>C here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Overall
CADD	11.68	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.Leu78=
Coding: c.232C>T
MANE Select: NM_030662
dbSNP: rs2041238210
Type: single nucleotide variant
Location: chr19:4117490 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 78: the protein kinase domain; a β-strand; a binding site

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.Gly132Asp Pathogenic/Likely pathogenic ★★ same condition
MAP2K2 c.450+5G>A Uncertain significance ★★ same condition
MAP2K2 p.Ala355Val Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Ala358Val Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Ala380Val Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Arg193Gln Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Arg193Ter Uncertain significance ★★ same condition
MAP2K2 p.Arg238Trp 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-leu78 (accessed [today's date]).

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