Is MAP2K1 p.Pro326= (c.978C>A) pathogenic?

MAP2K1 p.Pro326= (c.978C>A) is classified Likely benign in MAP2K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-12). Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K1 p.Pro326= (c.978C>A)?

MAP2K1 p.Pro326= (c.978C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K1 p.Pro326= (c.978C>A) in the general population?

MAP2K1 p.Pro326= (c.978C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

MAP2K1 p.Pro326=

c.978C>A · rs538987451 · VCV2450873

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 2.7	GERP 2.1, phastCons 1
Overall
CADD	17.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 0.000124% 2/1,614,022 alleles · very rare exomes 1/1,461,808 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	8.47e-05%	1,179,956

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.Pro326=
Coding: c.978C>A
MANE Select: NM_002755
dbSNP: rs538987451
Type: single nucleotide variant
Location: chr15:66489232 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.05 · 99 PDB
Residue 326: the protein kinase domain

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.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
MAP2K1 p.Ile317Thr 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-pro326 (accessed [today's date]).

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