Is MAP2K1 p.Leu313= (c.937T>C) pathogenic?

MAP2K1 p.Leu313= (c.937T>C) is classified Likely benign in MAP2K1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-27). Very rare (popmax 0.00333%, amr); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K1 p.Leu313= (c.937T>C)?

MAP2K1 p.Leu313= (c.937T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K1 p.Leu313= (c.937T>C) in the general population?

MAP2K1 p.Leu313= (c.937T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

MAP2K1 p.Leu313=

c.937T>C · rs1464431466 · VCV2565494

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 0.12	GERP -3.2, phastCons 0.98
Overall
CADD	5.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,982 alleles · very rare exomes 0/1,461,856 · genomes 2/152,126 · 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: MAP2K1
Protein: p.Leu313=
Coding: c.937T>C
MANE Select: NM_002755
dbSNP: rs1464431466
Type: single nucleotide variant
Location: chr15:66487269 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.05 · 99 PDB
Residue 313: the protein kinase domain; an α-helix

Full MAP2K1 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

MAP2K1 p.Leu313Phe Uncertain significance ★★ ⚠ same residue
MAP2K1 p.Ala268Val Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Ala32Val Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Arg108Gln Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Arg291Gly Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Asp217Asn Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Asp267Glu Uncertain significance ★★ ⚠ same condition
MAP2K1 p.Ile107Val 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/map2k1-p-leu313 (accessed [today's date]).

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