MAP2K2 c.450+307C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.36%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +307 | deep intronic (+307 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.7 | GERP 0.26, phastCons 0.003 |
| Non-coding constraint | Z 4.00 | 1 kb window · o/e 0.77 · regional · uncalibrated |
| Overall | ||
| CADD | 2.986 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.36%
Middle Eastern · 4/294 alleles
Filtering AF
1.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.11%
Overall
0.768%
1,169/152,220 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.36% | 74 |
| European (non-Finnish) | 1.21% | 83 |
| Finnishnot grpmax-eligible | 1.04% | 96 |
| Remaining individualsnot grpmax-eligible | 0.757% | 132 |
| Admixed American | 0.622% | 161 |
| Ashkenazi Jewishnot grpmax-eligible | 0.605% | 165 |
| Amishnot grpmax-eligible | 0.549% | 182 |
| South Asian | 0.229% | 437 |
| African / African-American | 0.207% | 483 |
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
- Coding
- c.450+307C>A
- MANE Select
- NM_030662
- dbSNP
- rs62132103
- Type
- single nucleotide variant
- Location
- chr19:4110202 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
Similar variants
- MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same type
- MAP2K2 p.Phe57Cys Pathogenic ★★★ same type
- MAP2K2 p.Phe57Val Pathogenic ★★★ same type
- MAP2K2 p.Pro128Gln Pathogenic ★★★ same type
- MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same type
- MAP2K2 p.Tyr134His Pathogenic ★★★ same type
- MAP2K2 p.Arg231His Uncertain significance ★★★ ⚠ same type
- MAP2K2 p.Arg231Leu Uncertain significance ★★★ ⚠ same type
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-c-450-plus-307c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown