MAP2K2 p.Thr396=
c.1188G>A · rs370956574 · VCV2054532
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, sas)
Conditions
1
RASopathy
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 -3.9 | GERP -2.9 |
| Overall | ||
| CADD | 8.152 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
South Asian · 15/84,160 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00885%
Overall
0.00303%
47/1,551,824 alleles · ultra-rare
exomes 42/1,399,520 · genomes 5/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0178% | 5,611 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,055 |
| European (non-Finnish) | 0.00253% | 39,581 |
| African / African-American | 0.00136% | 73,266 |
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
- Protein
- p.Thr396=
- Coding
- c.1188G>A
- MANE Select
- NM_030662
- dbSNP
- rs370956574
- Type
- single nucleotide variant
- Location
- chr19:4090613 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 396
- a modified residue (phosphothreonine)
Similar variants
- MAP2K2 p.Thr396Met Uncertain significance ★★★ ⚠ same residue
- MAP2K2 p.Thr396fs Uncertain significance ★ same residue
- MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
- MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
- MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
- MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
- MAP2K2 p.Tyr134His Pathogenic ★★★ same condition
- MAP2K2 p.Arg231His 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-thr396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown