MAPK7 p.Val459=
c.1377C>T · rs137998051 · VCV735403
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, nfe)
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 · C>A here scores Δ0.88 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.74, phastCons 1 |
| Overall | ||
| CADD | 5.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
European (non-Finnish) · 584/1,180,036 alleles
Filtering AF
0.0461%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0448%
Overall
0.0376%
607/1,613,824 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| African / African-American | 0.00934% | 10,706 |
| Finnishnot grpmax-eligible | 0.00784% | 12,758 |
| Admixed American | 0.00167% | 59,986 |
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
- MAPK7
- Protein
- p.Val459=
- Coding
- c.1377C>T
- MANE Select
- NM_002749
- dbSNP
- rs137998051
- Type
- single nucleotide variant
- Location
- chr17:19381586 (GRCh38)
- Gene constraint
- LOEUF 0.689 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.87 · 14 PDB
- Residue 459
- the 'disordered' region; the 'may not be required for kinase activity; required to stimulate mef2c activity' region
Similar variants
- MAPK7 p.Pro551Ser Benign/Likely benign ★★ same type
- MAPK7 p.Ala288Ser Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala29Gly Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala334Thr Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala348Ser Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala360Val Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala481Ser Uncertain significance ★ ⚠ same type
- MAPK7 p.Ala497Val 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/mapk7-p-val459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown